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1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1350309

RESUMO

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.


Assuntos
Humanos , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Neoplasias Hepáticas , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Regulação para Cima , Proteínas de Ligação a DNA , Variações do Número de Cópias de DNA
2.
Cell Commun Signal ; 20(1): 14, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090497

RESUMO

Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract.


Assuntos
Vesículas Extracelulares , Neoplasias , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias/metabolismo , Microambiente Tumoral
3.
Cytopathology ; 33(1): 14-22, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333812

RESUMO

There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting.


Assuntos
Neoplasias Pulmonares , Neoplasias Pleurais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Citodiagnóstico , Humanos , Neoplasias Pulmonares/patologia , Pleura/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia
4.
Diagn Cytopathol ; 50(3): 123-132, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34981669

RESUMO

BACKGROUND: Bile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases. MATERIALS AND METHODS: We re-evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer. RESULTS: The criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively. CONCLUSION: The criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.


Assuntos
Neoplasias dos Ductos Biliares , Bile , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Proteínas de Ligação a RNA/análise
5.
Clin. transl. oncol. (Print) ; 24(9): 1715-1731, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-505

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the fourth major cause of cancer-related death, with high morbidity and increased mortality year by year. Although significant progress has been made in the therapy strategies for CRC, the great difficulty in early diagnosis, feeble susceptibility to radiotherapy and chemotherapy, and high recurrence rates have reduced therapeutic efficacy resulting in poor prognosis. Therefore, it is urgent to understand the pathogenesis of CRC and unravel novel biomarkers to improve the early diagnosis, treatment and prediction of CRC recurrence. Long non-coding RNAs (lncRNAs) are non-coding RNAs with a length of more than 200 nucleotides, which are abnormally expressed in tumor tissues and cell lines, activating or inhibiting specific genes through multiple mechanisms including transcription and translation. A growing number of studies have shown that lncRNAs are important regulators of microRNAs (miRNAs, miRs) expression in CRC and may be promising biomarkers and potential therapeutic targets in the research field of CRC. This review mainly summarizes the potential application value of lncRNAs as novel biomarkers in CRC diagnosis, radiotherapy, chemotherapy and prognosis. Additionally, the significance of lncRNA SNHGs family and lncRNA–miRNA networks in regulating the occurrence and development of CRC is mentioned, aiming to provide some insights for understanding the pathogenesis of CRC and developing new diagnostic and therapeutic strategies. (AU)


Assuntos
Humanos , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , MicroRNAs/genética , Prognóstico
6.
Clin. transl. oncol. (Print) ; 24(9): 1818–1827, septiembre 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-JHG-514

RESUMO

BackgroundTumor-associated macrophages (TAM) are known to facilitate colorectal cancer (CRC) growth. High macrophage infiltration in thymidine phosphorylase (TYMP) expressing CRC may correspond to poor prognosis. The prognostic impact of the expression CD163, a receptor associated with TAM, and TYMP in stroma, respectively, tumor tissue is not yet established. The aim of this study was to identify the potential associations between TYMP and CD163 expression levels and relapse-free survival (RFS) of patients with stage II CRC, and if microdissection is of importance.MethodsStage II CRC patients, radically resected with relapse (n = 104), were matched to patients with a 5-year relapse-free follow-up (n = 206). Gene expression of TYMP and CD163 was analyzed in snap-frozen tumor tissues and in microdissected formalin-fixed tumor tissues separated into tumor epithelium and stroma.ResultsTYMP expression was high in poorly differentiated tumors, right-sided CRC, and tumors with high microsatellite instability CD163-expressing macrophages near tumor epithelial cells had high expression in poorly differentiated and T4 tumors. High TYMP expression in tumor epithelial cells was in the multivariate analyses associated with shorter relapse-free survival (hazard ratio 1.66; 95% confidence interval: 1.09–2.56; p < 0.05).ConclusionsTYMP expression in tumor epithelial cells was associated with RFS and emphasizes the need for tissue microdissection. Additional studies are needed to establish whether TYMP and CD163 could add clinically relevant information to identify high-risk stage II patients that could benefit from adjuvant chemotherapy. (AU)


Assuntos
Humanos , Antígenos CD/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Receptores de Superfície Celular , Prognóstico
8.
Eur Rev Med Pharmacol Sci ; 26(14): 5014-5032, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35916798

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death, with high morbidity and low survival. Research on the relationship between cancer cells and oxidative stress has rapidly increased in recent years. Therefore, finding new therapeutic and prognostic targets for hepatocellular carcinoma based on oxidative stress-related genes (OSRGs) has far-reaching significance. MATERIALS AND METHODS: We first obtained OSRGs on GeneCards and then, based on the TCGA database, compared tumor tissues with normal tissues. Using the LASSO Cox regression method, we obtained six differentially expressed genes associated with prognosis. We also divided all HCC patients in the TCGA cohort into a low-risk group and a high-risk group based on these six genes and accordingly performed a correlation analysis of differentially expressed oxidative-stress-related genes (DEOSRGs). These analyses included GSEA, PPI, survival analysis, immune correlation analysis, tumor microenvironment correlation analysis, m6A analysis, gene mutation analysis, drug-sensitivity analysis, and molecular docking validation. The reliability of the model genes was further verified using a multi-platform database, qRT-PCR and MTT assay. RESULTS: These six genes may play an important role in the prognosis of hepatocellular carcinoma patients by affecting the kinase, carboxylic acid synthesis and metabolism, ROS production, lipid oxidation and immune response. Validation experiment results further confirm that these model genes are good indicators for the diagnosis and prognosis of hepatocellular carcinoma. CONCLUSIONS: This study analyzed the prognosis and function of HCC prognosis-related differential genes, predicted that the prognosis-related differential genes played an essential role in HCC immunity, and proposed therapeutic targets and biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica/métodos , Humanos , Imunoterapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Simulação de Acoplamento Molecular , Estresse Oxidativo , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genética
9.
Sci Rep ; 12(1): 13503, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931808

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to "LXR/RXR and FXR/RXR Activation", "Acute Phase Response Signaling" in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify "low-risk" patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
World J Surg Oncol ; 20(1): 252, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932027

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients. METHODS: The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients. RESULTS: A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis. CONCLUSIONS: Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Biologia Computacional , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico
11.
J Mol Diagn ; 24(8): 867-877, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35934321

RESUMO

Detection of serum embryonic miRNAs miR-371a-3p and miR-372-3p has been proposed to aid in diagnosis, prognosis, and management of patients with testicular germ cell tumors (GCTs). This study describes the analytical validation and performance of a laboratory-developed test to detect these miRNA targets by stem loop real-time quantitative RT-PCR (RT-qPCR) in serum from patients with GCTs. The assay was standardized using an exogenous spike-in control of nonhuman miRNA from Caenorhabditis elegans (cel-miR-39-3p) to assess extraction efficiency, and an endogenous housekeeping miRNA, miR-30b-5p, to control for miRNA normalization. miRNA results were expressed as relative expression level, using the comparative threshold cycle method (2ΔΔCT). Analytical sensitivity of miR-371a-3p and miR-372-3p was 12.5 and 1.25 copies/µL, respectively. Clinical accuracy was evaluated using GCT patients with (n = 34) and without (n = 17) active disease. Positive/negative cutoffs and indeterminate findings were established on the basis of results from healthy volunteers (n = 25) and assay precision. miR-371a-3p and miR-372-3p exhibited a sensitivity of 81.8% and 87.5%, respectively, and a specificity of 100% and 94%, respectively, and an area under the receiver operating characteristic curve of 0.93 and 0.95, respectively. Taken together, RT-qPCR testing for serum miR-371a-3p and miR-372-3p represents a robust, sensitive, and specific clinical assay to aid in the clinical management of patients with GCT.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Biomarcadores Tumorais/genética , Humanos , Laboratórios Clínicos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares
12.
Anal Chim Acta ; 1221: 340136, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934407

RESUMO

MicroRNAs (miRNAs) are considered as biomarkers and display great potential in the diagnosis of diseases. As a colorectal cancer (CRC)-associated miRNA biomarker, miR-92a-3p possesses higher concentration in exosomes than in serum, causing it more feasible to diagnose CRC by measuring the concentration of miR-92a-3p inside exosomes. Herein, a rationally-engineered ratiometric fluorescent biosensor is proposed to detect the concentration of exosomal miR-92a-3p. The metal-organic framework (MOF-525) with self-fluorescence serves as both a fluorescent reference and a quencher of the fluorescence of single-stranded reporter by adsorption. The presence of miR-92a-3p triggers the looping of 5P-template strand and the further periodic rolling circle amplification. The periodic long strands and the reporters can form double strands to prevent the reporters from being adsorbed by MOF-525. The concentration of miR-92a-3p is positively correlated with the Δreporter/MOF-525 fluorescence intensity ratio. The biosensor exhibits a detection range of 0.1-10 pM and can differentiate miR-92a-3p from mismatched RNA sequences. The accuracy and practicality of the proposed biosensor for exosomal miRNA detection were evaluated by comparing with the conventional RT-qPCR. The as-obtained results are close to those of the RT-qPCR. This ratiometric fluorescent biosensor holds the potential for the sensitive detection of exosomal miRNA.


Assuntos
Técnicas Biossensoriais , Exossomos , MicroRNAs , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , Exossomos/química , MicroRNAs/análise
13.
Contrast Media Mol Imaging ; 2022: 6094409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935308

RESUMO

Purpose: The aim of this study is to explore the diagnostic value of prostate-specific antigen (PSA) combined with serum miRNA-149 expression in prostate cancer (PCa) by conducting experiments and bioinformatics analysis. Patients and Methods. 50 PCa patients were enrolled on the experimental group from January 2020 to December 2021. 56 patients with benign prostatic hyperplasia (BPH) were selected as the control group at the same time. Real-time fluorescent quantitative PCR was applied to investigate the miRNA-149 expression. PSA was detected by using a chemiluminescence meter using Abbott i4000. Applying bioinformatics analysis, we explored the expression of hsa-miR-149 in PCa in The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analyses were used to evaluate the prognostic value, and the ROC curve was applied. Results: The expression level of miRNA-149 in the PCa group was significantly higher than that in the BPH group (P < 0.05). The PSA level in the PCa group was also significantly higher than that in the BPH group (P < 0.05). TCGA data analysis revealed that PCa tissues had significantly increased hsa-miR-149 expression. The results of survival analysis showed that patients with high expression of hsa-miR-149 had better prognosis. Additionally, the pathological N stage of PCa correlates with the hsa-miR-149 expression level (P = 0.002). According to ROC curve analysis, the region under the curve was 0.653, 95% CI: 0.576-0.730. Conclusion: High expression of serum miRNA-149 is associated with PCa patients. Although combined PSA did not improve the diagnostic efficacy, miRNA-149 has high specificity in the diagnosis of PCa. miRNA-149 might be a novel marker for early diagnosis and prognosis assessment for PCa.


Assuntos
MicroRNAs , Hiperplasia Prostática , Neoplasias da Próstata , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
14.
Front Immunol ; 13: 946468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935965

RESUMO

TP53, a gene with high-frequency mutations, plays an important role in breast cancer (BC) development through metabolic regulation, but the relationship between TP53 mutation and metabolism in BC remains to be explored. Our study included 1,066 BC samples from The Cancer Genome Atlas (TCGA) database, 415 BC cases from the Gene Expression Omnibus (GEO) database, and two immunotherapy cohorts. We identified 92 metabolic genes associated with TP53 mutations by differential expression analysis between TP53 mutant and wild-type groups. Univariate Cox analysis was performed to evaluate the prognostic effects of 24 TP53 mutation-related metabolic genes. By unsupervised clustering and other bioinformatics methods, the survival differences and immunometabolism characteristics of the distinct clusters were illustrated. In a training set from TCGA cohort, we employed the least absolute shrinkage and selection operator (LASSO) regression method to construct a metabolic gene prognostic model associated with TP53 mutations, and the GEO cohort served as an external validation set. Based on bioinformatics, the connections between risk score and survival prognosis, tumor microenvironment (TME), immunotherapy response, metabolic activity, clinical characteristics, and gene characteristics were further analyzed. It is imperative to note that our model is a powerful and robust prognosis factor in comparison to other traditional clinical features and also has high accuracy and clinical usefulness validated by receiver operating characteristic (ROC) and decision curve analysis (DCA). Our findings deepen our understanding of the immune and metabolic characteristics underlying the TP53 mutant metabolic gene profile in BC, laying a foundation for the exploration of potential therapies targeting metabolic pathways. In addition, our model has promising predictive value in the prognosis of BC.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Feminino , Humanos , Mutação , Prognóstico , Curva ROC , Microambiente Tumoral/genética , Proteína Supressora de Tumor p53/genética
15.
Front Immunol ; 13: 947712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935970

RESUMO

Objective: It has been controversial whether tumor mutation burden (TMB) affects the prognosis and the efficacy of immunotherapy in different tumor types. We provided a comprehensive analysis of mutation status and immune landscape of squamous cell carcinomas (SCCs) from four sites in order to investigate the relationship of TMB with prognosis and immune cell infiltration in different SCCs. Methods: The transcriptome profiles and somatic mutation data of SCCs downloaded from the Cancer Genome Atlas (the Cancer Genome Atlas) database were analyzed and visualized. Then, TMB was calculated to analyze its correlations with prognosis and clinical features. Differentially expressed genes (DEGs) between the high and low TMB groups were screened for functional enrichment analysis. CIBERSORT algorithm was used to compare differences of immune cell infiltration between two groups in different SCCs. In addition, immune DEGs associated with prognosis were identified and risk prediction model was constructed via Cox regression analysis. Results: Missense mutation was the most dominant mutation type in SCCs. The difference was that the top10 mutated genes varied widely among different SCCs. High TMB group had better prognosis in lung squamous cell carcinoma (LUSC) and cervical squamous cell carcinoma (CESC), while the result was reverse in head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC). In addition, patients with older age, smoking history, earlier pathological stage and no lymphatic invasion had higher TMB. The identified DEGs were mainly enriched in the regulation of immune system, muscular system and the activity of epidermal cells. The proportions of CD8+T cells, CD4+ memory T cells, follicular helper T cells, macrophages were distinct between two groups. The prognosis-related hub genes (CHGB, INHBA, LCN1 and VEGFC) screened were associated with poor prognosis. Conclusion: This study reveals the mutation status and immune cell infiltration of SCCs at different anatomical sites. TMB is closely related to the prognosis of SCCs, and its effects on prognosis are diverse in different SCCs, which might result from the situation of immune cell infiltration. These findings contribute to the exploration of biomarkers for predicting the efficacy of immunotherapy in SCCs and providing innovative insights for accurate application of immunotherapy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/patologia , Mutação
16.
Front Immunol ; 13: 948601, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935976

RESUMO

Breast cancer (BC) is the most common malignancy worldwide and neoadjuvant therapy (NAT) plays an important role in the treatment of patients with early BC. However, only a subset of BC patients can achieve pathological complete response (pCR) and benefit from NAT. It is therefore necessary to predict the responses to NAT. Although many models to predict the response to NAT based on gene expression determined by the microarray platform have been proposed, their applications in clinical practice are limited due to the data normalization methods during model building and the disadvantages of the microarray platform compared with the RNA-seq platform. In this study, we first reconfirmed the correlation between immune profiles and pCR in an RNA-seq dataset. Then, we employed multiple machine learning algorithms and a model stacking strategy to build an immunological gene based model (Ipredictor model) and an immunological gene and receptor status based model ICpredictor model) in the RNA-seq dataset. The areas under the receiver operator characteristic curves for the Ipredictor model and ICpredictor models were 0.745 and 0.769 in an independent external test set based on the RNA-seq platform, and were 0.716 and 0.752 in another independent external test set based on the microarray platform. Furthermore, we found that the predictive score of the Ipredictor model was correlated with immune microenvironment and genomic aberration markers. These results demonstrated that the models can accurately predict the response to NAT for BC patients and will contribute to individualized therapy.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Aprendizado de Máquina , Microambiente Tumoral/genética
17.
Front Immunol ; 13: 928742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935979

RESUMO

Although costimulatory molecules have been shown to boost antitumor immune responses, their significance in stomach adenocarcinoma (STAD) remains unknown. The purpose of this study was to examine the gene expression patterns of costimulatory molecule genes in patients with STAD and develop a predictive signature to aid in therapy selection and outcome prediction. We used 60 costimulatory family genes from prior research to conduct the first complete costimulatory molecular analysis in patients with STAD. In the two study groups, consensus clustering analysis based on these 60 genes indicated unique distribution patterns and prognostic differences. Using the least absolute shrinkage and selection operator and Cox regression analysis, we identified nine costimulatory molecular gene pairs (CMGPs) with prognostic value. With these nine CMGPs, we were able to develop a costimulatory molecule-related prognostic signature that performed well in an external dataset. For the patients with STAD, the signature was proven to be a risk factor independent of the clinical characteristics, indicating that this signature may be employed in conjunction with clinical considerations. A further connection between the signature and immunotherapy response was discovered. The patients with high mutation rates, an abundance of infiltrating immune cells, and an immunosuppressive milieu were classified as high-risk patients. It is possible that these high-risk patients have a better prognosis for immunotherapy since they have higher cytolytic activity scores and immunophenoscores of CTLA4 and PD-L1/PD-L2 blockers. Therefore, our signature may help clinicians in assessing patient prognosis and developing treatment plans.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico , Neoplasias Gástricas/patologia , Fatores de Transcrição
18.
Front Immunol ; 13: 916915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936000

RESUMO

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.


Assuntos
Fibrossarcoma , Microambiente Tumoral , Biomarcadores Tumorais/genética , Fibrossarcoma/genética , Fibrossarcoma/terapia , Humanos , Imunoterapia , Prognóstico
19.
BMC Cancer ; 22(1): 862, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933332

RESUMO

BACKGROUND: Cervical cancer is a preventable disease, but it is a major public health problem despite having a good prognosis when diagnosed early. Although the Pap smear has led to huge drops in rates of cervical cancer and death from the disease, it has some limitations, making new approaches necessary for early diagnosis and biomarkers discovery. MiRNAs have been considered a new class of non-invasive biomarkers and may have great clinical value for screening early-stage cervical intraepithelial neoplasia. Well-designed studies have emerged as a necessary strategy for the identification of miRNAs that could be used safely and reliably for a differential diagnosis. This review aims to provide an up-to-date perspective on the assessment of circulating miRNA expression from precursor lesions to cervical cancer, identifying circulating miRNAs or specific miRNA signatures that can be used as potential biomarkers of different stages of cervical carcinogenesis. METHODS: A systematic review was performed and searches were conducted in the PubMed, LILACS, and Scopus electronic databases. RESULTS: Most studies involved Chinese ethnic women and searched for circulating miRNAs in serum samples. Thirty three microRNAs were evaluated in the eligible studies and 17 (miR-196a, miR-16-2, miR-497, miR-1290, miR-425-5p, hsa-miR- 92a, miR-1266, miR-9, miR-192, miR-205, miR-21, miR-152, miR-15b, miR-34a, miR-218, miR-199a-5p and miR-155-5p) showed up-regulation in women with precursor lesion and cervical cancer and 16 microRNAs showed decreased expression in these same groups of women compared to healthy controls (miR-195, miR-2861, miR-145, miR-214, miR-34a, miR-200a, let-7d-3p, miR-30d-5p, miR-638, miR-203a-3p, miR-1914-5p, miR-521, miR-125b, miR-370, miR-218 and miR-100). CONCLUSION: Therefore, defining promising circulating miRNAs or specific miRNA signatures of biological fluid samples can be useful for the screening, diagnosis, prognosis and clinical monitoring of women undergoing cervical carcinogenesis, but greater standardization of studies seems to be necessary for greater consolidation of information.


Assuntos
MicroRNA Circulante , MicroRNAs , Neoplasias do Colo do Útero , Biomarcadores , Biomarcadores Tumorais/genética , Carcinogênese/genética , Detecção Precoce de Câncer , Feminino , Humanos , MicroRNAs/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética
20.
BMC Med Genomics ; 15(1): 174, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933370

RESUMO

BACKGROUND: TIR domain containing adaptor molecule 1 (TICAM1) is a coding gene participating in immune and inflammation responses to malignant cells. However, the role of TICAM1 in Wilms tumor (WT) is rarely known. MATERIALS AND METHODS: The expression level of TICAM1 was calculated in the WT TARGET cohort and validated using the GSE66405 cohort. The Kaplan-Meier method was employed to investigate the potential clinical value of TICAM1 and the association between its expression level and clinical features. The influence of TICAM1 on immune infiltration was examined by ESTIMATE, CIBERSORT and MCPcounter algorithms. IC50 of chemotherapeutic drugs was calculated by "pRRophetic" R package. RESULTS: TICAM1 was downregulated in WT patients with worse prognosis and a more advanced clinical stage. Moreover, a low expression level of TICAM1 contributed to less immune cell infiltration, few protective immune cells and more antitumor immune cells. CONCLUSIONS: TICAM1 exerts a significant impact on the prognosis, progression and immune infiltration condition of WT.


Assuntos
Neoplasias Renais , Tumor de Wilms , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Biomarcadores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Tolerância Imunológica , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Prognóstico , Tumor de Wilms/genética , Tumor de Wilms/patologia
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