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1.
BMC Med Genomics ; 15(1): 225, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316684

RESUMO

OBJECTIVE: Gastric carcinoma is the most common malignant tumour of the human digestive system worldwide. CD44 serves as a marker for several tumour stem cells, including gastric cancer. However, the prognostic value of CD44 and its correlation with immune infiltration in gastric cancer remain unclear. METHODS: The relative expression level of CD44 RNA in gastric cancer was analysed in the TCGA and GEPIA2 databases and validated in the GEO database. Differences in CD44 between gastric cancer cell lines and normal cells were detected by real-time PCR, and the HPA database was used to analyse the differential expression of CD44 protein in gastric cancer and normal tissues. The effect of CD44 on the proliferation and migration of gastric cancer cells was detected by CCK8 and transwell assays. UALCAN was used to analyse the relationship between CD44 expression and clinical parameters, and the Kaplan‒Meier Plotter was used to evaluate the prognostic value, including overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS). The CD44 gene and protein interaction network was constructed by using the Linked Omics, GeneMANIA, STRING and DisGeNET databases. GO and KEGG analyses and GSEA of CD44 were performed by using R language. The correlation between CD44 and immune infiltration was explored by using the TIMER, CIBERSORT and GEPIA databases. RESULTS: CD44 is highly expressed in gastric cancer compared with normal tissues. Inhibition of proliferation and migration of gastric cancer cells after CD44 knockdown was observed. The UALCAN database showed that CD44 was independent of sex in gastric cancer but correlated with cancer stage and lymph node metastasis. Kaplan‒Meier Plotter online analysis showed that OS, PFS and PPS were prolonged in the CD44 low-expression group. GO and KEGG analyses and GSEA results showed that CD44 was mainly located in the endoplasmic reticulum and the extracellular matrix containing collagen, which was mainly involved in protein digestion and absorption. TIMER, CIBERSORT and GEPIA showed that CD44 was associated with infiltrating immune cells and thereby affected survival prognosis. CONCLUSION: CD44 is highly expressed in gastric cancer and is an independent prognostic factor associated with immune invasion, which can be used as a candidate prognostic biomarker to determine the prognosis associated with gastric immune invasion.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Prognóstico , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Receptores de Hialuronatos
2.
Front Immunol ; 13: 994259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341373

RESUMO

Background: Hepatocellular carcinoma (HCC) is an aggressive and heterogeneous disease characterized by high morbidity and mortality. The liver is the vital organ that participates in tyrosine catabolism, and abnormal tyrosine metabolism could cause various diseases, including HCC. Besides, the tumor immune microenvironment is involved in carcinogenesis and can influence the patients' clinical outcomes. However, the potential role of tyrosine metabolism pattern and immune molecular signature is poorly understood in HCC. Methods: Gene expression, somatic mutations, copy number variation data, and clinicopathological information of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. GSE14520 from the Gene Expression Omnibus (GEO) databases was used as a validation dataset. We performed unsupervised consensus clustering of tyrosine metabolism-related genes (TRGs) and classified patients into distinct molecular subtypes. We used ESTIMATE algorithms to evaluate the immune infiltration. We then applied LASSO Cox regression to establish the TRGs risk model and validated its predictive performance. Results: In this study, we first described the alterations of 42 TRGs in HCC cohorts and characterized the clinicopathological characteristics and tumor microenvironmental landscape of the two distinct subtypes. We then established a tyrosine metabolism-related scoring system and identified five TRGs, which were highly correlated with prognosis and representative of this gene set, namely METTL6, GSTZ1, ADH4, ADH1A, and LCMT1. Patients in the high-risk group had an inferior prognosis. Univariate and multivariate Cox proportional hazards regression analysis also showed that the tyrosine metabolism-related signature was an independent prognostic indicator. Besides, receiver operating characteristic curve (ROC) analysis demonstrated the predictive accuracy of the TRGs signature that could reliably predict 1-, 3-, and 5-year survival in both TCGA and GEO cohorts. We also got consistent results by performing clone formation and invasion analysis, and immunohistochemical (IHC) assays. Moreover, we also discovered that the TRGs signature was significantly associated with the different immune landscapes and therapeutic drug sensitivity. Conclusion: Our comprehensive analysis revealed the potential molecular signature and clinical utilities of TRGs in HCC. The model based on five TRGs can accurately predict the survival outcomes of HCC, improving our knowledge of TRGs in HCC and paving a new path for guiding risk stratification and treatment strategy development for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Microambiente Tumoral/genética , Neoplasias Hepáticas/patologia , Variações do Número de Cópias de DNA , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Tirosina , Glutationa Transferase/genética
3.
BMC Gastroenterol ; 22(1): 450, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344926

RESUMO

Hepatocellular carcinoma (HCC) is the most common neoplasm and the major cause of cancer-associated death worldwide. The high mortality rate of HCC is mainly attributed to its widespread prevalence and the lack of effective treatment. Immunotherapy as a promising, innovative approach has revolutionised the treatment of solid tumours. However, owing to the heterogeneity and complex tumour microenvironment of HCC, an efficient biomarker for immunotherapy has yet to be identified. We investigated the role of immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in patients with HCC from The Cancer Genome Atlas (TCGA) database. Spearman correlation, univariate and multivariate Cox, and lasso regression analyses were utilised to screen lncRNAs associated with prognosis. Four lncRNAs were filtered out to develop an immune-associated lncRNA prognostic signature in TCGA training as well as validation cohorts. Patients with HCC were then categorised into low- and high-risk groups according to the median value of the risk scores to evaluate the ability of the prognostic model between training and validation cohorts. A nomogram (based on risk score and stage) was constructed to appraise the general overall survival (OS) of patients with HCC. Differences in immune cell infiltration, immune checkpoint inhibitor (ICI) treatment response, gene mutation, and drug sensitivity were observed between the two groups. Thus, the lncRNA prognostic signature can serve as a sensitive prognostic biomarker with potential in individualised immunotherapy for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Longo não Codificante/genética , Prognóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Estimativa de Kaplan-Meier , Microambiente Tumoral
4.
J Int Med Res ; 50(11): 3000605221135864, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36366735

RESUMO

OBJECTIVE: High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 (HOXA9) is linked with serous papillary histotype differentiation, and inappropriate HOXA9 expression is a step in ovarian cancer that induces aberrant differentiation. This study aimed to reveal the significance of HOXA9 in HGSOC. METHODS: HOXA9 mRNA and protein expression were examined by quantitative PCR and immunohistochemistry, respectively. The chi-square test was used to evaluate associations between HOXA9 expression and clinical characteristics. The prognostic value of HOXA9 was calculated by the Kaplan-Meier method. The Kaplan-Meier Plotter database was used to assess the prognostic value of HOXA9. RESULTS: The mRNA and protein expression of HOXA9 were significantly upregulated in chemotherapy-resistant HGSOC compared with chemotherapy-sensitive HGSOC. The chi-square test showed that high HOXA9 expression was significantly related with grade, clinical stage, and residual disease. High HOXA9 expression was significantly associated with poor prognosis. The Kaplan-Meier Plotter database further confirmed these results. Cox hazard regression showed that high HOXA9 expression was an independent prognostic factor for survival in HGSOC patients. CONCLUSION: This study showed that HOXA9 expression was associated with chemotherapy resistance and poor outcomes in HGSOC patients. High HOXA9 expression might be a prognostic indicator for HGSOC.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Estimativa de Kaplan-Meier , Prognóstico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Expressão Gênica , RNA Mensageiro/genética
5.
BMC Pulm Med ; 22(1): 404, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344955

RESUMO

BACKGROUND: Surgical resection is usually recommended for the treatment of pulmonary sclerosing pneumocytoma (PSP). However, no comparative study has demonstrated that surgical resection leads to improved outcomes. We aimed to compare all-cause mortality between patients with PSP who underwent surgery or did not and those without PSP. METHODS: Participants aged ≥18 years who had pathologically diagnosed PSP between 2001 to 2018, at 3 hospitals were included. Randomly selected (up to 1:5) age-, sex-, and smoking status-matched controls without PSP who were randomly selected from those who underwent health checkups including chest CT were included. Mortality was compared using Kaplan-Meier estimates and Cox proportional hazards regression models. Literature review of studies reporting PSP was also conducted. RESULTS: This study included 107 patients with PSP (surgery:non-surgery, 80:27) and 520 matched controls. There were no cases of lymph node or distant metastasis, recurrence, or mortality from PSP. No significant difference in all-cause mortality risk was observed between the PSP surgery, PSP non-surgery, and non-PSP groups (log rank test P = 0.78) (PSP surgery vs. non-PSP: adjusted hazards ratio [aHR], 1.80; 95% confidence interval [CI], 0.22-14.6; PSP non-surgery vs. non-PSP: aHR, 0.77; 95% CI, 0.15-3.86; PSP surgery vs. PSP non-surgery: aHR, 2.35; 95% CI, 0.20-28.2). In the literature review, we identified 3469 patients with PSP from 355 studies. Only 1.33% of these patients reported metastasis, recurrence, or death. CONCLUSIONS: All-cause mortality did not differ between patients with PSP and those without, irrespective of undergoing surgery. Our study and the literature review suggest that PSP has less impact on increased mortality risk.


Assuntos
Hemangioma Esclerosante Pulmonar , Humanos , Adolescente , Adulto , Hemangioma Esclerosante Pulmonar/cirurgia , Hemangioma Esclerosante Pulmonar/diagnóstico , Hemangioma Esclerosante Pulmonar/patologia , Pulmão/patologia , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X , Estudos Retrospectivos
6.
Medicine (Baltimore) ; 101(44): e31302, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343057

RESUMO

At present, there is no systematic study on the signature of long-chain noncoding RNAs (lncRNAs) involved in metabolism that can fully predict the prognosis in patients with low-grade gliomas (LGGs). Therefore, consistent metabolic-related lncRNA signatures need to be established. The Cancer Genome Atlas (TCGA) was used to identify the expression profile of lncRNAs containing 529 LGGs samples. LncRNAs and genes related to metabolism are used to establish a network in the form of coexpression to screen lncRNAs related to metabolism. LncRNA was more clearly described by univariate Cox regression. Moreover, lncRNA signatures were explored by multivariate Cox regression and lasso regression. The risk score was established according to the signature and it was an unattached prognostic marker according to Cox regression analysis. Functional enrichment of lncRNAs was shown by employing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Univariate Cox retrospective analysis showed that 543 metabolism-related lncRNAs were independent prognostic factors of LGG, and multivariate Cox regression analysis confirmed that 19 metabolism-related lncRNAs were prognostic genes of LGG. In the risk model, the low-risk group had a higher Overall survival (OS) than the high-risk group (P < .001). Univariate Cox regression analysis of risk score and clinical factors showed that risk score was an independent prognostic factor (P < .001, HR = 1.047, 95% CI: 1.038-1.056). Multivariate Cox results showed that risk score could predict the prognosis of LGG (P < .001, HR = 1.036, 95% CI: 1.026-1.045). ROC curve analysis showed that risk score could predict the prognosis of LGG. The areas of 1-year, 3-years, and 5 years are 0.891, 0.904 and 0.832. GO and KEGG analysis showed that metabolism-related lncRNAs was mainly concentrated in the pathways related to tumor metabolism. In order to find a more stable and reliable target for the treatment of LGG, we established 19 metabolic-related lncRNAs prognostic model, and determined that it can predict the prognosis of LGG patients. This provides a new solution approach to the poor prognosis of patients with LGG and may reverse the trend of LGG's transformation to high-grade gliomas.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Prognóstico , Glioma/genética
7.
Respir Res ; 23(1): 306, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357897

RESUMO

BACKGROUND: Ubiquitin-conjugating enzyme E2 T (UBE2T) is a potential oncogene. However, Pan-cancer analyses of the functional, prognostic and predictive implications of this gene are lacking. METHODS: We first analyzed UBE2T across 33 tumor types in The Cancer Genome Atlas (TCGA) project. We investigated the expression level of UBE2T and its effect on prognosis using the TCGA database. The correlation between UBE2T and cell cycle in pan-cancer was investigated using the single-cell sequencing data in Cancer Single-cell State Atlas (CancerSEA) database. The Weighted Gene Co-expression Network analysis (WGCNA), Univariate Cox and Least absolute shrinkage and selection operator (LASSO) Cox regression models, and receiver operating characteristic (ROC) were applied to assess the prognostic impact of UBE2T-related cell cycle genes (UrCCGs). Furthermore, the consensus clustering (CC) method was adopted to divide TCGA-lung adenocarcinoma (LUAD) patients into subgroups based on UrCCGs. Prognosis, molecular characteristics, and the immune panorama of subgroups were analyzed using Single-sample Gene Set Enrichment Analysis (ssGSEA). Results derived from TCGA-LUAD patients were validated in International Cancer Genome Consortium (ICGC)-LUAD data. RESULTS: UBE2T is highly expressed and is a prognostic risk factor in most tumors. CancerSEA database analysis revealed that UBE2T was positively associated with the cell cycle in various cancers(r > 0.60, p < 0.001). The risk signature of UrCCGs can reliably predict the prognosis of LUAD (AUC1 year = 0.720, AUC3 year = 0.700, AUC5 year = 0.630). The CC method classified the TCGA-LUAD cohort into 4 UrCCG subtypes (G1-G4). Kaplan-Meier survival analysis demonstrated that G2 and G4 subtypes had worse survival than G3 (Log-rank test PTCGA training set < 0.001, PICGC validation set < 0.001). A comprehensive analysis of immune infiltrates, immune checkpoints, and immunogenic cell death modulators unveiled different immune landscapes for the four subtypes. High immunophenoscore in G3 and G4 tumors suggested that these two subtypes were immunologically "hot," tending to respond to immunotherapy compared to G2 subtypes (p < 0.001). CONCLUSIONS: UBE2T is a critical oncogene in many cancers. Moreover, UrCCG classified the LUAD cohort into four subgroups with significantly different survival, molecular features, immune infiltrates, and immunotherapy responses. UBE2T may be a therapeutic target and predictor of prognosis and immunotherapy sensitivity.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Enzimas de Conjugação de Ubiquitina/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Estimativa de Kaplan-Meier
8.
Front Immunol ; 13: 1018942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341390

RESUMO

Objective: Increasing studies have indicated that senescence was associated with tumorigenesis and progression. Lower-grade glioma (LGG) presented a less invasive nature, however, its treatment efficacy and prognosis prediction remained challenging due to the intrinsic heterogeneity. Therefore, we established a senescence-related signature and investigated its prognostic role in LGGs. Methods: The gene expression data and clinicopathologic features were from The Cancer Genome Atlas (TCGA) database. The experimentally validated senescence genes (SnGs) from the CellAge database were obtained. Then LASSO regression has been performed to build a prognostic model. Cox regression and Kaplan-Meier survival curves were performed to investigate the prognostic value of the SnG-risk score. A nomogram model has been constructed for outcome prediction. Immunological analyses were further performed. Data from the Chinese Glioma Genome Atlas (CGGA), Repository of Molecular Brain Neoplasia Data (REMBRANDT), and GSE16011 were used for validation. Results: The 6-SnG signature has been established. The results showed SnG-risk score could be considered as an independent predictor for LGG patients (HR=2.763, 95%CI=1.660-4.599, P<0.001). The high SnG-risk score indicated a worse outcome in LGG (P<0.001). Immune analysis showed a positive correlation between the SnG-risk score and immune infiltration level, and the expression of immune checkpoints. The CGGA datasets confirmed the prognostic role of the SnG-risk score. And Kaplan-Meier analyses in the additional datasets (CGGA, REMBRANDT, and GSE16011) validated the prognostic role of the SnG-signature (P<0.001 for all). Conclusion: The SnG-related prognostic model could predict the survival of LGG accurately. This study proposed a novel indicator for predicting the prognosis of LGG and provided potential therapeutic targets.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Glioma/patologia , Neoplasias Encefálicas/patologia , Estimativa de Kaplan-Meier
9.
Genes (Basel) ; 13(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36360316

RESUMO

A new treatment modality targeting cuproptosis is gradually entering the public horizon. Cuproptosis is a new form of regulated cell death distinct from ferroptosis, apoptosis, autophagy, and necrosis. Previous studies have discovered that the copper level varies considerably in various cancers and that an increase in copper content is directly associated with the proliferation and metastasis of cancer cells. In non-small cell lung cancer (NSCLC) after radiation, the potential utility of cuproptosis-related long noncoding RNAs (lncRNAs) is still unclear. This research aimed to develop a prediction signature based on lncRNAs associated with cuproptosis to predict the prognosis of NSCLC patients following radiation. Methods: Expression data of primary tumors and adjacent solid tissues were downloaded from The Cancer Genome Atlas (TCGA) database, along with the corresponding clinical and mutational data. Univariate and multivariate COX analyses and LASSO regression analyses were performed to obtain a predictive signature of lncRNAs associated with cuproptosis. The data were randomly grouped into a training group used for model construction and a test group used for model validation. The model was validated by drawing a survival curve, risk curve, independent prognostic analysis, ROC curve PFS analysis, etc. Results: The lncRNA signature consisting of six cuproptosis-related lncRNAs (AC104088.1, PPP4R3B-DT, AC006042.3, LUCAT1, HHLA3-AS1, and LINC02029) was used to predict the prognosis of patients. Among them, there were three high-risk lncRNAs (LUCAT1, HHLA3-AS1, and LINC02029) with HR > 1 and three protective lncRNAs (AC104088.1, PPP4R3B-DT, and AC006042.3), with an HR < 1. Data analysis demonstrated that the cuproptosis-related lncRNA signatures could well predict the prognosis of NSCLC patients after radiation. Patients in the high-risk category receive a worse prognosis than those in the low-risk group. Cuproptosis-related risk prediction demonstrated better predictive qualities than age, gender, and pathological stage factors. Conclusion: The risk proposed model can independently predict the prognosis of NSCLC patients after radiotherapy, provide a foundation for the role of cuproptosis-related lncRNAs in NSCLC after radiotherapy, and provide a clinical strategy for radiotherapy combined with cuproptosis in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Regulação Neoplásica da Expressão Gênica , Cobre/metabolismo , Estimativa de Kaplan-Meier , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia
10.
Biomed Res Int ; 2022: 9710540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330457

RESUMO

Background: Several cancers, including lung adenocarcinoma (LUAD), are caused by genes related to necroptosis. However, it is still unknown how necroptosis-related long noncoding RNAs (lncRNAs) may be involved in LUAD. In order to predict the prognosis of LUAD patients and personalize immunotherapy, this study set out to construct a necroptosis-related lncRNA prognostic signature (NLPS). Methods: The Cancer Genome Atlas (TCGA) database was used to download the LUAD transcriptome data and the associated clinical data. lncRNAs associated with necroptosis were screened using coexpression analysis. An NLPS was built using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The Gene Expression Omnibus (GEO) database's GSE30219 was used to validate the NLPS. The prognostic value of the risk score was assessed using Kaplan-Meier survival, receiver operating characteristic (ROC) Cox regression, multivariate Cox regression, and nomogram analyses. Then, we looked into the differences between the low- and high-risk groups in the tumor immune microenvironment, immunotherapy response, and half-maximal inhibitory concentration (IC50). Results: The 14 lncRNAs in a novel NLPS were created. With further validation in the GSE30219 dataset, the risk score according to the NLPS was an independent prognostic indicator for LUAD patients. Patients with better overall survival (OS) in the low-risk group, who were characterized by increased immune cell infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS), may have hot tumors and higher immunotherapy response rates. In addition, the risk score was also closely linked to sensitivity to various anticancer medications. Conclusions: We constructed a novel NLPS that could predict OS and sensitivity to immunotherapy in LUAD patients.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Prognóstico , Necroptose/genética , Regulação Neoplásica da Expressão Gênica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Pulmão/patologia , Microambiente Tumoral/genética
11.
JMIR Public Health Surveill ; 8(11): e40386, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36378507

RESUMO

BACKGROUND: Stage-specific survival, according to the eighth edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on breast cancer (BC), between Chinese and White American women remains unclear. OBJECTIVE: This study aimed to assess stage-specific survival in BC between Chinese and White American women according to the eighth AJCC PPS. METHODS: We included Chinese and White American women with BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. A chi-square test, the Kaplan-Meier method, a receiver operating characteristic (ROC) curve, and multivariate Cox proportional hazards models were used for data analysis. RESULTS: We included 376,818 individuals in this study: 369,522 White American and 7296 Chinese. Of them, 149,452 (39.7%) migrated from the seventh AJCC anatomic staging (AS) to the eighth AJCC PPS, 22,516 (6.0%) were upstaged, and 126,936 (33.7%) were downstaged. With a median follow-up duration of 44 months, the 5-year overall survival and cancer-specific survival (CSS) for the entire group were 87.4% and 95.9%, respectively. The seventh AJCC AS (P<.001) and the eighth AJCC PPS (P<.001) could significantly predict the survival outcomes of BC, and multivariate analysis revealed that both staging systems were significant prognostic indicators of CSS. The ROC curve revealed that the PPS had a better discriminating ability than the AS (area under the curve [AUC] 0.769 vs 0.753, P<.001). Similar trends were observed after stratification by the 2 ethnic groups. The eighth AJCC PPS had better discriminating ability than the seventh AJCC AS among both White American (AUC 0.769 vs 0.753, P<.001) and Chinese patients (AUC 0.790 vs 0.776, P<.001). In the seventh AJCC AS, Chinese women had better CSS in stage IA (P=.02), stage IIA (P=.005), and stage IIIB (P=.04) disease than White American women, but no significant CSS was observed in stage IB, IIB, IIIA, and IIIC disease between the 2 ethnic groups. Regarding the eighth AJCC PPS, Chinese women had better CSS in stage IA (P=.002) and IIIA (P=.046) disease than White American women, and CSS was similar in Chinese and White American women in other substages. CONCLUSIONS: The eighth AJCC PPS has a similar discriminative ability between White American and Chinese individuals with BC compared with the seventh AJCC AS. Therefore, the eighth AJCC PPS is also applicable to Chinese individuals with BC.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Estadiamento de Neoplasias , Estimativa de Kaplan-Meier , Análise de Dados , Brancos , China/epidemiologia
12.
Front Immunol ; 13: 961695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389709

RESUMO

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients. Methods: Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Results: We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments. Conclusion: The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Estimativa de Kaplan-Meier , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Canais Iônicos/genética , Microambiente Tumoral/genética , Canal de Sódio Disparado por Voltagem NAV1.4
13.
Sci Rep ; 12(1): 19857, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400857

RESUMO

Lung adenocarcinoma (LUAD) is one of the most universal types of cancer all over the world and its morbidity continues to rise year by year. Growing evidence has demonstrated that endoplasmic reticulum stress is highly activated in cancer cells and plays a key role in regulating the fate of cancer cells. However, the role and mechanism of endoplasmic reticulum stress in lung adenocarcinoma genesis and development remains unclear. In this research, we developed a prognostic model to predict the overall survival of patients with LUAD utilizing endoplasmic reticulum stress-related genes and screened out potential small molecular compounds, which could assist the clinician in making accurate decisions and better treat LUAD patients. Firstly, we downloaded 419 endoplasmic reticulum stress-related genes (ERSRGs) from Molecular Signatures Database (MSigDB). Secondly, we obtained information about the transcriptome profiling and corresponding clinical data of 59 normal samples and 535 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database. Next, we used the DESeq2 package to identify differentially expressed genes related to endoplasmic reticulum stress. We performed univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis to establish a prognostic model for LUAD patients based on ERSRGs. Then, we carried out univariate and multivariate independent prognostic analysis of endoplasmic reticulum stress-related gene (ERSRG) score and some clinical traits of lung adenocarcinoma. Additionally, we developed a clinically applicable nomogram for predicting survival for LUAD patients over one, three, and five years. Moreover, we carried out a drug sensitivity analysis to identify novel small molecule compounds for LUAD treatment. Finally, we examined the tumor microenvironment (TME) and immune cell infiltrating analysis to explore the interactions between immune and cancer cells. 142 differentially expressed ERSRGs were identified by using the DESeq2 package. A prognostic model was built based on 7 differentially expressed ERSRGs after performing univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. According to the results of univariate and multivariate independent prognostic analysis, we found ERSRG score can be used as an independent prognostic maker. Using the Kaplan-Meier curves, we found low-risk patients had higher survival probability than high-risk patients in both training set and test set. A nomogram was drawn to predict 1-, 3-, and 5-year survival probability. The calibration curves explained good performance of the model for the prediction of survival. Phenformin, OSU-03012, GSK-650394 and KIN001-135 were identified as the drugs most likely to provide important information to clinicians about the treatment of LUAD patients. A prognostic prediction model was established based on 7 differentially expressed ERSRGs (PDX1, IGFBP1, DDIT4, PPP1R3G, CFTR, DERL3 and NUPR1), which could effectively predict the prognosis of LUAD patients and give a reference for clinical doctors to help LUAD patients to make better treatment tactics. Based on the 4 small molecule compounds (Phenformin, OSU-03012, GSK-650394 and KIN001-135) we discovered, targeting endoplasmic reticulum stress-related genes may also be a therapeutic approach for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Estresse do Retículo Endoplasmático/genética , Fenformin , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estimativa de Kaplan-Meier , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Microambiente Tumoral
14.
Sci Rep ; 12(1): 19923, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402820

RESUMO

The purpose of the present research was to assess the prognostic impact of marital status in hepatocellular carcinoma (HCC) patients with tumors ≤ 2 cm (stage Ia) based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received a histopathologic HCC diagnosis between 2004 and 2016 were recruited. Overall survival (OS) was the major outcome measure. The Cox regression model and the Fine-Gray regression model were used for the purpose of comparing and examining the prognostic value of marital status for OS. The data for a total of 2446 stage Ia HCC patients were extracted from the database. The median overall survival time was 96.0 months, with 5-year and 10-year overall survival rates of 58.2% and 45.8%, respectively. In both the Fine-Gray regression model and Cox regression model, marital status [married vs. unmarried and others, both P < 0.001, hazard ratio (HR) = 1.389 for Cox and HR = 1.378 for Fine-Gray], age at diagnosis, tumor grade, and surgery at the primary site independently served as prognostic indicators associated with OS. In conclusion, positive marital status was independently associated with better OS for stage Ia HCC patients, and its prognostic influence should be validated in the near future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Programa de SEER , Neoplasias Hepáticas/patologia , Estimativa de Kaplan-Meier , Estado Civil
15.
Pathol Oncol Res ; 28: 1610396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388433

RESUMO

Background: Typically, liver cancer patients are diagnosed at an advanced stage and have a poor prognosis. N-recognin 5 (UBR5), a component of the ubiquitin protein ligase E3, is involved in the genesis and progression of several types of cancer. As of yet, it is unknown what the exact biological function of UBR5 is in liver cancer. Methods: A Kaplan-Meier survival curve (OS) was used to examine the effect of UBR5 expression on overall survival based on the TCGA database. To determine the molecular functions of UBR5 in liver cancer, we used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A protein-protein interaction (PPI) network was established for the screening of UBR5-related proteins in liver cancer. Western blot analysis was used to determine the expression levels of UBR5 and YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta), and in order to detect cell proliferation, an MTT assay was used. Results: The expression of UBR5 in liver cancer patient samples is significantly higher than in adjacent normal tissues. A high level of UBR5 expression was associated with older patients, a higher tumor grade, lymph node metastasis, and poor survival. We discovered YWHAZ with high connectivity, and UBR5 expression correlated positively with YWHAZ expression (r = 0.83, p < 0.05). Furthermore, we found that elevated UBR5 levels directly correlated with YWHAZ overexpression, and that UBR5 promoted cell proliferation by affecting YWHAZ expression. Additionally, the TCGA databases confirmed that patients with liver cancer who expressed higher levels of YWHAZ had poorer outcomes. Conclusion: This suggests that UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and that UBR5 may be a candidate treatment target for liver cancer. Therefore, UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and UBR5 could serve as a potential target for liver cancer treatment.


Assuntos
Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/genética , Proliferação de Células/genética , Estimativa de Kaplan-Meier
16.
Sci Rep ; 12(1): 18688, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333388

RESUMO

Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has demonstrated that mitophagy is crucial to developing colorectal cancer. This study aims to examine the association between mitophagy-related genes and the prognosis of CRC patients. Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied to establish a prognostic signature using mitophagy related genes. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to analyze patient survival and predictive accuracy. Meanwhile, we also used the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. ATG14 overexpression plasmid was used to regulate the ATG14 expression level in HCT116 and SW480 cell lines, and cell counting kit-8, colony formation and transwell migration assay were performed to validate the function of ATG14 in CRC cells. A total of 22 mitophagy-driven genes connected with CRC survival were identified, and then a novel prognostic signature was established based on 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter in both the training cohort and two independent cohorts. ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a Nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI 0.71-0.83) and more robust predictive accuracy. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more enriched in the high-risk group. Furthermore, patients in the high-risk group are more sensitive to targeted therapy or chemotherapy, including bosutinib, elesclomol, lenalidomide, midostaurin, pazopanib and sunitinib, while the low-risk group is more likely to benefit from immunotherapy. Finally, in vitro study confirmed the oncogenic significance of ATG14 in both HCT116 and SW480 cells, whose overexpression increased CRC cell proliferation, colony formation, and migration. In conclusion, we developed a novel mitophagy-related gene signature that can be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients, and we confirmed ATG14 as a novel oncogene in CRC.


Assuntos
Neoplasias Colorretais , Mitofagia , Humanos , Mitofagia/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Colorretais/patologia , Prognóstico , Microambiente Tumoral/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
17.
Eur Rev Med Pharmacol Sci ; 26(21): 7813-7826, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394729

RESUMO

OBJECTIVE: DEPDC1B, which encodes DEP domain-containing protein 1B, exerts pathogenic effects in diverse cancers, but no such effect has been reported in the case of lower-grade glioma (LGG). Therefore, we sought to investigate the relationship between DEPDC1B expression and the prognosis of patients with LGG and reveal the underlying molecular mechanism. MATERIALS AND METHODS: First, RT-qPCR and immunohistochemical staining were used to examine DEPDC1B mRNA and protein expression in LGG. Second, transcriptomic data were collected from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to investigate the impact of DEPDC1B expression on LGG patients by using the Kaplan-Meier survival analysis, receiver operating characteristic analysis and Cox models. Third, the effects of DEPDC1B on LGG cell proliferation and migration were revealed using wound-healing and Cell Counting Kit-8 assays and Ki67 immunofluorescence staining. Fourth, the Tumor Immune Estimation Resource database was used to examine how DEPDC1B affects the LGG immune microenvironment, and gene set enrichment analysis was used to uncover the signaling pathways in which DEPDC1B is involved in LGG. RESULTS: DEPDC1B was significantly upregulated in both LGG cells and tissues, and high expression of DEPDC1B contributed to poor prognosis of LGG patients and represented an independent risk factor for LGG. Moreover, DEPDC1B knockdown reduced the proliferation and migration abilities of LGG cells. Lastly, DEPDC1B was found to be positively associated with multiple immune infiltrates and immune-checkpoint markers. CONCLUSIONS: Our findings indicate for the first time that DEPDC1B is a pathogenic gene in LGG. More importantly, we provide a new biomarker and immunotherapeutic target for improving the diagnosis and treatment of LGG patients.


Assuntos
Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Prognóstico , Proliferação de Células , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Microambiente Tumoral , Proteínas Ativadoras de GTPase/genética
18.
Pathol Oncol Res ; 28: 1610538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405393

RESUMO

Background: The study aimed to detect DEGs associated with BRCA bone metastasis, filter prognosis biomarkers, and explore possible pathways. Methods: GSE175692 dataset was used to detect DEGs between BRCA bone metastatic cases and non-bone metastatic cases, followed by the construction of a PPI network among DEGs. The main module among the PPI network was then determined and pathway analysis on genes within the module was performed. Through performing Cox regression, Kaplan-Meier, nomogram, and ROC curve analyses using GSE175692 and GSE124647 datasets at the same time, the most significant prognostic biomarker was gradually filtered. Finally, important pathways associated with prognostic biomarkers were explored by GSEA analysis. Results: The 74 DEGs were detected between bone metastasis and non-bone metastasis groups. A total of 15 nodes were included in the main module among the whole PPI network and they mainly correlated with the IL-17 signaling pathway. We then performed Cox analysis on 15 genes using two datasets and only enrolled the genes with p < 0.05 in Cox analysis into the further analyses. Kaplan-Meier analyses using two datasets showed that the common biomarker AGR2 expression was related to the survival time of BRCA metastatic cases. Further, the nomogram determined the greatest contribution of AGR2 on the survival probability and the ROC curve revealed its optimal prognostic performance. More importantly, high expression of AGR2 prolonged the survival time of BRCA bone metastatic patients. These results all suggested the importance of AGR2 in metastatic BRCA. Finally, we performed the GSEA analysis and found that AGR2 was negatively related to IL-17 and NF-kß signaling pathways. Conclusion: AGR2 was finally determined as the most important prognostic biomarker in BRCA bone metastasis, and it may play a vital role in cancer progression by regulating IL-17 and NF-kB signaling pathways.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Interleucina-17 , Neoplasias Ósseas/genética , Estimativa de Kaplan-Meier , Mucoproteínas , Proteínas Oncogênicas
19.
Genes (Basel) ; 13(11)2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36360233

RESUMO

Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cancers, including breast cancer (BC). This study aimed to explore for the first time the association of the migration/differentiation-associated lncRNA SENCR rs12420823C/T variant with BC risk and prognosis. Genotyping was carried out for 203 participants (110 patients and 93 controls) using the TaqMan allelic discrimination technique. The corresponding clinicopathological data, including the recurrence/survival times, were analyzed with the different genotypes. After adjustment by age and risk factors, the T/T genotype carrier patients were more likely to develop BC under homozygote comparison (T/T vs. C/C: OR = 8.33, 95% CI = 2.44-25.0, p = 0.001), dominant (T/T-C/T vs. C/C: OR = 3.70, 95% CI = 1.72-8.33, p = 0.027), and recessive (T/T vs. C/T-C/C: OR = 2.17, 95% CI = 1.08-4.55, p < 0.001) models. Multivariate logistic regression analysis showed that the T/T genotype carriers were more likely to be triple-negative sub-type (OR = 2.66, 95% CI = 1.02-6.95, p = 0.046), at a higher risk of recurrence (OR = 3.57, 95% CI = 1.33-9.59, p = 0.012), and had short survival times (OR = 3.9, 95% CI = 1.52-10.05, p = 0.005). Moreover, Cox regression analysis supported their twofold increased risk of recurrence (HR = 2.14, 95% CI = 1.27-3.59, p = 0.004). Furthermore, the predictive nomogram confirmed the high weight for SENCR rs12420823*T/T and C/T genotypes in predicting recurrence within the first year. The Kaplan-Meier survival curve demonstrated low disease-free survival (T/T: 12.5 ± 1.16 months and C/T: 15.9 ± 0.86 months versus C/C: 22.3 ± 0.61 months, p < 0.001). In conclusion, the LncRNA SENCR rs12420823*C/T may be associated with an increased risk of BC in women and could be a promising genetic variant for predicting recurrence and survival.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Prognóstico , RNA Longo não Codificante/genética
20.
Biol Direct ; 17(1): 29, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36319976

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although marker genes associated with CRC have been identified previously, only a few have fulfilled the therapeutic demand. Therefore, based on differentially expressed genes (DEGs), this study aimed to establish a promising and valuable signature model to diagnose CRC and predict patient's prognosis. METHODS: The key genes were screened from DEGs to establish a multiscale embedded gene co-expression network, protein-protein interaction network, and survival analysis. A support vector machine (SVM) diagnostic model was constructed by a supervised classification algorithm. Univariate Cox analysis was performed to construct two prognostic signatures for overall survival and disease-free survival by Kaplan-Meier analysis, respectively. Independent clinical prognostic indicators were identified, followed by univariable and multivariable Cox analysis. GSEA was used to evaluate the gene enrichment analysis and CIBERSORT was used to estimate the immune cell infiltration. Finally, key genes were validated by qPCR and IHC. RESULTS: In this study, four key genes (DKC1, FLNA, CSE1L and NSUN5) were screened. The SVM diagnostic model, consisting of 4-gene signature, showed a good performance for the diagnostic (AUC = 0.9956). Meanwhile, the four-gene signature was also used to construct a risk score prognostic model for disease-free survival (DFS) and overall survival (OS), and the results indicated that the prognostic model performed best in predicting the DFS and OS of CRC patients. The risk score was validated as an independent prognostic factor to exhibit the accurate survival prediction for OS according to the independent prognostic value. Furthermore, immune cell infiltration analysis demonstrated that the high-risk group had a higher proportion of macrophages M0, and T cells CD4 memory resting was significantly higher in the low-risk group than in the high-risk group. In addition, functional analysis indicated that WNT and other four cancer-related signaling pathways were the most significantly enriched pathways in the high-risk group. Finally, qRT-PCR and IHC results demonstrated that the high expression of DKC1, CSE1L and NSUN5, and the low expression of FLNA were risk factors of CRC patients with a poor prognosis. CONCLUSION: In this study, diagnosis and prognosis models were constructed based on the screened genes of DKC1, FLNA, CSE1L and NSUN5. The four-gene signature exhibited an excellent ability in CRC diagnosis and prognostic prediction. Our study supported and highlighted that the four-gene signature is conducive to better prognostic risk stratification and potential therapeutic targets for CRC patients.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Humanos , Biomarcadores Tumorais/genética , Prognóstico , Estimativa de Kaplan-Meier , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
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