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1.
PLoS Comput Biol ; 17(8): e1009224, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34383739

RESUMO

Computational integrative analysis has become a significant approach in the data-driven exploration of biological problems. Many integration methods for cancer subtyping have been proposed, but evaluating these methods has become a complicated problem due to the lack of gold standards. Moreover, questions of practical importance remain to be addressed regarding the impact of selecting appropriate data types and combinations on the performance of integrative studies. Here, we constructed three classes of benchmarking datasets of nine cancers in TCGA by considering all the eleven combinations of four multi-omics data types. Using these datasets, we conducted a comprehensive evaluation of ten representative integration methods for cancer subtyping in terms of accuracy measured by combining both clustering accuracy and clinical significance, robustness, and computational efficiency. We subsequently investigated the influence of different omics data on cancer subtyping and the effectiveness of their combinations. Refuting the widely held intuition that incorporating more types of omics data always produces better results, our analyses showed that there are situations where integrating more omics data negatively impacts the performance of integration methods. Our analyses also suggested several effective combinations for most cancers under our studies, which may be of particular interest to researchers in omics data analysis.

2.
Clin Immunol ; 229: 108800, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34289424

RESUMO

The study aimed to investigate the soluble programmed death-1 (sPD-1) and its ligand (sPD-L1) levels in systemic juvenile idiopathic arthritis (sJIA) patients and elucidate its underlying immunomodulatory mechanisms. Plasma levels of sPD-1, sPD-L1 and related cytokines and proteins were detected using an enzyme-linked immunosorbent assay (ELISA) and Luminex. The effects of PD-1/PD-L1 signal on mDC (myeloid dendritic cell) and IL-6 secretion were measured using flow cytometry. The results revealed decreased levels of sPD-1 in sJIA patients negatively correlated with JADAS-27, PGA, PtGA and CRP. sJIA patients had lower CD86 and MHC-II expression on mDC. When blocking PD-1/PD-L1 signal, IL-6 secretion of DC were increased. Our finding displayed downregulated sPD-1 was related with clinical indicators and could be a new biomarker for sJIA diagnosis. The reduced membrane and soluble forms of PD-1/PD-L1 might take part in sJIA pathogenesis by enhancing mDC proliferation and IL-6 secretion.


Assuntos
Artrite Juvenil/imunologia , Antígeno B7-H1/imunologia , Receptor de Morte Celular Programada 1/imunologia , Artrite Juvenil/sangue , Artrite Juvenil/diagnóstico , Antígeno B7-H1/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/sangue , Células Dendríticas/imunologia , Regulação para Baixo , Feminino , Humanos , Interleucina-6/sangue , Masculino , Receptor de Morte Celular Programada 1/sangue , Transdução de Sinais/imunologia , Solubilidade
3.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 195-204, 2021 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-34137226

RESUMO

To evaluate the therapeutic effect of using micro-implant anchorage (MIA) to rotate the functional occlusal plane (FOP) counterclockwise. Forty skeletal class Ⅱ high-angle patients who had completed orthodontic treatment were enrolled, including 20 patients treated with MIA orthodontic system (MIA group) and the other 20 patients treated with traditional sliding straight wire appliance (control group). Cephalometric measurements on the lateral cranial radiographs before and after treatment were performed, all acquired data were statistically analyzed with SPSS 26.0. At the end of treatment, MIA group obtained better effect of FOP and mandibular plane counter-clockwise rotation than the control group. In the MIA group, the average change of FOP-frankfort horizontal plane (FH), FOP-SN and mandibular plane angle (MP-FH) angle was -4.5(-7.3, -3.7)°, (3.3)° and -1.7(-3.0, -0.9)°, respectively. In the control group, the average change of FOP-FH, FOP-SN and MP-FH angle was -0.1(-4.1, 3.0)°, (-0.1±5.1)° and -0.4(-2.4, 0.7)°, respectively. There was significant difference between the change of the two groups (all <0.05). Compared with the traditional sliding straight wire appliance, counterclockwise rotation of FOP can be more effectively reversed by using MIA orthodontic system, and the MP-FH can be reduced as well.


Assuntos
Oclusão Dentária , Má Oclusão Classe II de Angle , Cefalometria , Humanos , Má Oclusão Classe II de Angle/terapia , Mandíbula , Maxila , Resultado do Tratamento
4.
Brief Bioinform ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33940590

RESUMO

Single-cell clustering is an important part of analyzing single-cell RNA-sequencing data. However, the accuracy and robustness of existing methods are disturbed by noise. One promising approach for addressing this challenge is integrating pathway information, which can alleviate noise and improve performance. In this work, we studied the impact on accuracy and robustness of existing single-cell clustering methods by integrating pathways. We collected 10 state-of-the-art single-cell clustering methods, 26 scRNA-seq datasets and four pathway databases, combined the AUCell method and the similarity network fusion to integrate pathway data and scRNA-seq data, and introduced three accuracy indicators, three noise generation strategies and robustness indicators. Experiments on this framework showed that integrating pathways can significantly improve the accuracy and robustness of most single-cell clustering methods.

5.
Sleep Breath ; 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33893906

RESUMO

PURPOSE: The previous analysis of systematic reviews and meta-analyses have illustrated that obstructive sleep apnea (OSA) is correlated with multiple health outcomes. In the present research, our main aim was to execute an umbrella review to assess the available evidence for the associations between OSA and health outcomes. METHODS: Herein, a meta-analysis of previous observational investigations that have reported associations between OSA and health outcomes in all human populations and settings was performed. We used these studies to execute an umbrella review of available meta-analyses and systematic reviews. RESULTS: Sixty-six articles comprising 136 unique outcomes were enrolled in this analysis. Of the 136 unique outcomes, 111 unique outcomes had significant associations (p < 0.05). Only 7 outcomes (coronary revascularization after PCI, postoperative respiratory failure, steatosis, alaninetrans aminase (ALT) elevation, metabolic syndrome (MS), psoriasis, and Parkinson's disease) had a high quality of evidence. Twenty-four outcomes had a moderate quality of evidence, and the remaining 80 outcomes had a weak quality of evidence. Sixty-nine outcomes exhibited significant heterogeneity. Twenty-five outcomes exhibited publication bias. Sixty-three (95%) studies showed critically low methodological quality. CONCLUSION: Among the 66 meta-analyses exploring 136 unique outcomes, only 7 statistically significant outcomes were rated as high quality of evidence. OSA may correlate with an increased risk of coronary revascularization after PCI, postoperative respiratory failure, steatosis, ALT elevation, MS, psoriasis, and Parkinson's disease.

6.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33398336

RESUMO

BACKGROUND: Several studies have assessed the relationship between long non-coding RNA five prime to Xist (FTX) expression, clinicopathological features, and survival outcomes in patients with cancer with conflicting results. This meta-analysis synthesized existing data to clarify the association between FTX with cancer prognosis. METHODS: PubMed, Embase, Cochrane library, Web of Science, Chinese CNKI, and the Chinese WanFang databases were used to search for relevant studies. The role of FTX in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Eleven studies comprising 1210 participants including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), renal cell carcinoma (RCC), osteosarcoma (OSC), and glioma were enrolled in this analysis. The meta-analysis showed that high FTX expression was significantly associated with several clinicopathological characteristics, including lymph node metastasis in patients with CRC, GC, HCC, and RCC, distant metastasis in patients with CRC, GC, HCC, and OSC, larger tumor size in patients with CRC, GC, HCC, RCC, and OSC, and subsequently TNM/clinical stage in patients with CRC, GC, HCC, OSC, and glioma. The pooled results from the survival analysis revealed a significant correlation between high FTX expression and shorter OS in patients with HCC, CRC, GC, OSC, and glioma. Further, FTX overexpression could be an independent predictive marker for shorter OS in patients with CRC, HCC, OSC, and glioma. CONCLUSIONS: FTX may be a potential oncogene, with high FTX expression being associated with a poorer prognosis in patients with CRC, HCC, OSC, and glioma.

7.
Biomarkers ; 26(2): 95-102, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33401971

RESUMO

OBJECTIVE: To assess the diagnostic value of Trefoil factor 3 (TFF3) and the correlation between TFF3 expression and clinicopathological features in patients with gastric cancer (GC). METHODS: PubMed, The Cochrane, EMbase, and Web of Science were retrieved comprehensively to collect relevant literature. The search ended on 31 May 2020. All data were analyzed using PubMed, The Cochrane, EMbase, and Web of Science were retrieved to collect relevant articles. All data from the included studies were subjected to meta-analysis using Stata 12.0 software. RESULTS: Seventeen studies involved 4654 subjects were included. For the diagnostic value of TFF3 for GC, the sensitivity, specificity, and AUC were 0.71, 0.80, and 0.80, respectively. For the clinicopathological value of TFF3, tissue TFF3 expression showed a higher risk of lymph node metastasis (OR 2.20, 95% CI 1.75-2.78, p < 0.001) and muscularis propria invasion (≥T2) (1.51, 1.13-2.03, p = 0.006), as well as worse TNM stage (2.26, 1.63-3.12, p < 0.001) and histological type (1.72, 1.34-2.20, p < 0.001), while no apparent relationship was found for serous membrane invasion (T4), venous invasion, and peritoneal metastasis. CONCLUSION: TFF3 may be a promising biomarker for GC, and the TFF3 expression is likely to be involved in the invasion, metastasis, and differentiation of GC.

8.
J Microbiol Immunol Infect ; 54(2): 206-212, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31204209

RESUMO

BACKGROUND: Interleukin 6 (IL-6) induce the inflammatory response directly related with the morbidity and mortality of neonatal. Here we aimed to explore the mechanism of IL-6 in neonatal inflammatory response by studying the IL-6/STAT3 signaling pathway. METHODS: Cord blood samples from health term neonatal and peripheral venous blood from health volunteers were collected. The monocytes of adults and cord blood were isolated and induced into macrophages. Then the macrophages were pretreated with or without MG132 before IL-6 stimulation. Proteins were analyzed by Western blot, mRNA by real time PCR and membrane molecule by flow cytometry. RESULTS: The acute phase protein gene expression in neonatal macrophages after stimulated with IL-6 were higher than that in adult. Significantly enhanced phosphorylation of STAT3 was seen in neonatal macrophages. Both mRNA and protein expression of SOCS3 in neonatal macrophages were lower than that in adult. After pretreated with MG132, the expression of SOCS3 protein was increased which lead to attenuate the STAT3 phosphorylation and APP gene expression. CONCLUSION: Neonatal exhibit an enhanced expression of downstream target genes and IL-6/STAT3 signal pathway which is related with the diminished SOCS3. This provides a new sight into inflammatory responses in neonatal.

9.
Protein Expr Purif ; 178: 105782, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33122039

RESUMO

Streptococcus pneumoniae is a gram-positive bacterial pathogen causing invasive pneumonia, meningitis, otitis media, and bacteremia. Owing to the current pitfalls of polysaccharide and polysaccharide-conjugate vaccines, protein vaccines are considered promising candidates against pneumonia. Pneumococcal surface protein A (PspA) and pneumococcal surface adhesin A (PsaA) are virulence proteins showing good immunogenicity and protective effects against S. pneumoniae strains in mice. In this study, we expressed the fusion protein PsaA-PspA, which consists of PsaA and the N-terminal region of PspA family 1 and 2, in Escherichia coli. We describe a novel and effective method to purify PsaA-PspA using hydroxyapatite and two-step chromatography. After determining the optimal induction conditions and a series of purification steps, we obtained PsaA-PspA fusion protein with over 95% purity at a final yield of 22.44% from the starting cell lysate. The molecular weight of PsaA-PspA was approximately 83.6 kDa and its secondary structure was evaluated by circular dichroism. Immunization with the purified protein induced high levels of IgG antibodies in mice. Collectively, these results demonstrate that our purification method can effectively produce high-purity PsaA-PspA fusion protein with biological activity and chemical integrity, which can be widely applied to the purification of other PspA subclass proteins.


Assuntos
Adesinas Bacterianas , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias , Imunoglobulina G/imunologia , Proteínas Recombinantes de Fusão , Streptococcus pneumoniae/imunologia , Adesinas Bacterianas/química , Adesinas Bacterianas/imunologia , Adesinas Bacterianas/isolamento & purificação , Adesinas Bacterianas/farmacologia , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/farmacologia , Escherichia coli , Feminino , Expressão Gênica , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/farmacologia
10.
BMC Bioinformatics ; 21(1): 433, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008305

RESUMO

BACKGROUND: Precise disease module is conducive to understanding the molecular mechanism of disease causation and identifying drug targets. However, due to the fragmentization of disease module in incomplete human interactome, how to determine connectivity pattern and detect a complete neighbourhood of disease based on this is still an open question. RESULTS: In this paper, we perform exploratory analysis leading to an important observation that through a few intermediate nodes, most separate connected components formed by disease-associated proteins can be effectively connected and eventually form a complete disease module. And based on the topological properties of these intermediate nodes, we propose a connect separate connected components (C3) method to detect a succinct disease module by introducing a relatively small number of intermediate nodes, which allows us to obtain more pure disease module than other methods. Then we apply C3 across a large corpus of diseases to validate this connectivity pattern of disease module. Furthermore, the connectivity of the perturbed genes in multi-omics data such as The Cancer Genome Atlas also fits this pattern. CONCLUSIONS: C3 tool is not only useful in detecting a clearly-defined connected disease neighbourhood of 299 diseases and cancer with multi-omics data, but also helpful in better understanding the interconnection of phenotypically related genes in different omics data and studying complex pathological processes.


Assuntos
Algoritmos , Doença , Asma/genética , Neoplasias da Mama/genética , Feminino , Ontologia Genética , Humanos , Anotação de Sequência Molecular , Mapas de Interação de Proteínas , Proteínas/metabolismo
11.
Mol Med Rep ; 22(5): 4101-4106, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000236

RESUMO

Yes­associated protein (YAP) acts as a transcriptional co­activator in gene expression and cell proliferation control by binding to the transcriptional factor TEA domain (TEAD) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co­activator, ß­catenin of the Wnt signaling pathway. Whether YAP preferentially acts as a transcriptional co­regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type. Nuclear YAP upregulates the expression of ß­catenin, while cytoplasmic YAP has a negative effect on this expression. The present mini­review focused on the important roles of YAP and further discussed the cross­links between the Wnt and Hippo signaling pathways. The Wnt and Hippo signaling pathways are both related to the development of fibrosis or cancer. The current review discussed treatment approaches for these conditions based on the two pathways. YAP, the intersection of these two signaling pathways, has the potential to be developed as a novel treatment target, according to previous basic studies on fibroblasts and cancer cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Fibrose , Regulação da Expressão Gênica , Humanos , Especificidade de Órgãos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Wnt/metabolismo
12.
Int Immunopharmacol ; 89(Pt A): 107053, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045568

RESUMO

Lung squamous cell carcinoma (LUSC) is the most common histologic type of smoking-related non-small cell lung cancer (NSCLC). However, there are no identified potential biomarkers for smoking-related LUSC diagnosis and prognosis. Especially, the characteristics of genetic alteration and tumor microenvironment induced by cigarette smoking remain unknown. Here, we performed integrative analysis of 463 LUSC with smoking history information from The Cancer Genome Atlas (TCGA). Non-smokers had the best prognosis, and current reformed smokers had better overall survival (OS) than current smokers in all and stage I-II cohort. Then, pathway enrichment analysis might suggest that smoking may play a role in regulating tumor metabolism and invasion and metastasis via those pathways. We constructed an eight-gene signature and identified WNT7A, Solute carrier-7A5 (SLC7A5) and Brain­type glycogen phosphorylase (PYGB), which may be served as biomarkers related to the smoking. Notably, the single copy deletion of WNT7A and SLC17A5 and the low-level amplification of PYGB may be related to the epigenetic mechanism of smoking on tumorigenesis. We also estimated the relative proportion of 24 immune cell subtypes within tumor microenvironment in different smoking status. Interestingly, we found NK cells activated, NK cells resting and endothelial cells might play an important role in immunologic dysfunction and harmful tumor microenvironment induced by cigarette smoking. Our research has identified potential biomarkers for smoking-related LUSC diagnosis and prognosis, which would help to further understand the pathogenesis of LUSC.


Assuntos
Carcinoma de Células Escamosas/sangue , Genômica , Neoplasias Pulmonares/sangue , Fumar/efeitos adversos , Fumar/sangue , Biomarcadores/sangue , Carcinoma de Células Escamosas/metabolismo , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Mutação , Polimorfismo de Nucleotídeo Único
13.
Food Sci Nutr ; 8(8): 4196-4204, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884700

RESUMO

The methods to leaching juice from dried jujube using six treatments and some factors related with juice yield such as total soluble solids (TSS), pectinase activity, pectin contents, galacturonic acid, and the microstructure morphology of cell were investigated. Six treatments including natural leaching, ultrasonic, microwave, ultrasonic before microwave, ultrasonic after microwave, and pressing directly were applied to extract juice. The group which treating with ultrasonic before microwave displayed its total soluble solids (TSS) was 16 °Brix, which was 6.67% higher than that of natural leaching. And its total soluble solids (TSS) reached to equilibrium in 2 hr, which was faster than that of natural leaching. The mechanism of improving the production efficiency of juice yield using ultrasonic combined with microwave was explored accordingly. The content of pectin and galacturonic acid increased by 58.52% and 59.01%, respectively, which were the highest among all samples. The activity of pectinase was 9.71 µg/(h·g), which was significantly decreased 40.23% as compared to natural leaching. And the treated cells became shriveled and pitted, which led to the leakage of the contents of cell. Thus, the result showed that treating with ultrasonic before microwave displayed the best juice yield. Ultrasonic cooperate with microwave was an efficient method to leaching juice from dried jujube.

14.
Aging (Albany NY) ; 12(17): 17288-17294, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32915164

RESUMO

Genomic mutation may be key factors for sex-biased disparities in cancer diagnosis, prognosis and prediction of treatment response. Current study has revealed that sex-based dimorphism on the efficacy of immune checkpoint inhibitors (ICIs) in various cancers and confirmed that male patients can benefit more from immunotherapy. However, only a subset of male patients responds well to ICIs. Therefore, biomarkers are desperately needed to identify the group of patients who may be more likely to benefit from ICIs. With the availability of the cBioPortal database, we identified that TERT mutation may serve as a sex-specific cancer biomarker and TERT mutation frequency of melanoma was higher in male patients. Notably, we found that male patients with TERT mutation may be more likely to benefit from immunotherapy (p = 0.006), especially for melanoma (p < 0.001). Therefore, our research provides a possible direction for the exploration of immunotherapy prediction biomarkers based on sex difference.

15.
Cancer Med ; 9(19): 7151-7160, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810393

RESUMO

Immune checkpoint inhibitors (ICIs) have recently changed therapeutic paradigms for patients across multiple cancer types. However, current biomarkers cannot accurately predict responses to ICIs. Telomerase reverse transcriptase (TERT) mutations lead to an aberrant upregulation of TERT expression, and ultimately allow telomere maintenance, thus supporting immortalization of cancer cells. This study aimed to investigate whether the TERT mutation is a potential predictor of ICI treatment across all cancer types. TERT mutations positively correlated with a higher tumor mutational burden (TMB) value, neoantigen load, and tumor purity. Lymphocyte infiltration, macrophage regulation, interferon-gamma (IFN-γ) response, and transforming growth factor-ß (TGF-ß) response which was representative immune-expression signatures, all had higher signature scores in the TERT mutation group. Activated CD4 T cell, naïve B cell, activated dendritic cell, M0 macrophage, M1 macrophage, neutrophil, resting NK cell, and plasma cells all had relatively higher immune scores in the TERT mutation group, whereas Th series cells, memory B cell, resting mast cells, monocytes, and activated NK cells had lower immune scores. Notably, in the subgroup analysis of monotherapy and combination ICI treatment, only in the anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4) group, patients with TERT mutations had a better prognosis, especially for melanoma. Therefore, TERT mutations were closely related to a higher TMB value and unique tumor microenvironment, which may be the reason that TERT mutations may be a potential biomarker for anti-CTLA4 treatment.

16.
J Transl Autoimmun ; 3: 100046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32743527

RESUMO

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by chronic inflammation and pathogenic auto-antibodies. Apart from B cells, dysregulation of other immune cells also plays an essential role in the pathogenesis and development of the disease including CD4+T cells, dendritic cells, macrophages and neutrophils. Since metabolic programs control immune cell fate and function, they are critical checkpoints in an effective immune response and are involved in the etiology of autoimmune disease. In addition, mitochondria and oxidative stress are both involved in cellular metabolism and is also essential in immune response. In this review, apart from the disturbed immune system, we will discuss mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid and amino acid metabolism) of immune cells as well as epigenetic control of metabolism reprogramming to elucidate the underlying pathogenic mechanisms of systemic lupus erythematosus.

18.
Aging (Albany NY) ; 12(10): 9868-9881, 2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32445554

RESUMO

Long non-coding RNAs (lncRNAs) play an important role in various biological processes of lung adenocarcinoma (LUAD), such as immune response regulation, tumor microenvironment remodeling and genomic alteration. Nevertheless, immune-related lncRNAs and their immune and genomic alterations characteristics in LUAD samples still remain unreported. Here, using various public databases, statistic and software tools, we constructed two immune-related lncRNA clusters with different immune and genomic alterations characteristics. Notably, cluster 1 had a stronger immunosuppressive tumor microenvironment (TME) and a higher mutation frequency than cluster 2, especially the mutant genes, such as Kelch-like ECH-associated protein 1 (KEAP1) and toll like receptor 4 (TLR4). In cluster 1, both the amplified and deleted portions of copy number variation (CNV) segments were enriched and cyclin dependent kinase inhibitor 2A (CDKN2A) was significantly deleted. GSVA analysis revealed that these immune-related lncRNAs may be involved in stem cell and EMT functions. Furthermore, cluster 1 was related to worse prognosis of LUAD patients. Therefore, we constructed two immune-related and prognostic lncRNA clusters and identified their immune and genomic alterations characteristics in LUAD samples, which could well divide LUAD patients into different immune phenotypes and help to understand immune molecular mechanisms of LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Família Multigênica/imunologia , RNA Longo não Codificante/imunologia , Variações do Número de Cópias de DNA/imunologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Mutação/imunologia , Prognóstico , Modelos de Riscos Proporcionais , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
19.
JAMA Netw Open ; 3(4): e202950, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32267515

RESUMO

Importance: Information about stage of cancer at diagnosis, use of therapy, and survival among patients from different racial/ethnic groups with 1 of the most common cancers is lacking. Objective: To assess stage of cancer at diagnosis, use of therapy, overall survival (OS), and cancer-specific survival (CSS) in patients with cancer from different racial/ethnic groups. Design, Setting, and Participants: This cohort study included 950 377 Asian, black, white, and Hispanic patients who were diagnosed with prostate, ovarian, breast, stomach, pancreatic, lung, liver, esophageal, or colorectal cancers from January 2004 to December 2010. Data were collected using the Surveillance, Epidemiology, and End Results (SEER) database, and patients were observed for more than 5 years. Data analysis was conducted in July 2018. Main Outcomes and Measures: Multivariable logistic and Cox regression were used to evaluate the differences in stage of cancer at diagnosis, treatment, and survival among patients from different racial/ethnic groups. Results: A total of 950 377 patients (499 070 [52.5%] men) were included in the study, with 681 251 white patients (71.7%; mean [SD] age, 65 [12] years), 116 015 black patients (12.2%; mean [SD] age, 62 [12] years), 65 718 Asian patients (6.9%; mean [SD] age, 63 [13] years), and 87 393 Hispanic patients (9.2%; mean [SD] age, 61 [13] years). Compared with Asian patients, black patients were more likely to have metastatic disease at diagnosis (odds ratio [OR], 1.144; 95% CI, 1.109-1.180; P < .001). Black and Hispanic patients were less likely to receive definitive treatment than Asian patients (black: adjusted OR, 0.630; 95% CI, 0.609-0.653; P < .001; Hispanic: adjusted OR, 0.751; 95% CI, 0.724-0.780; P < .001). White, black, and Hispanic patients were more likely to have poorer CSS and OS than Asian patients (CSS, white: adjusted HR, 1.310; 95% CI, 1.283-1.338; P < .001; black: adjusted HR, 1.645; 95% CI, 1.605-1.685; P < .001; Hispanic: adjusted HR, 1.300; 95% CI, 1.266-1.334; P < .001; OS, white: adjusted HR, 1.333; 95% CI, 1.310-1.357; P < .001; black: adjusted HR, 1.754; 95% CI, 1.719-1.789; P < .001; Hispanic: adjusted HR, 1.279; 95% CI, 1.269-1.326; P < .001). Conclusions and Relevance: In this study of patients with 1 of 9 leading cancers, stage at diagnosis, treatment, and survival were different by race and ethnicity. These findings may help to optimize treatment and improve outcomes.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Razão de Chances , Fatores Raciais , Estados Unidos/etnologia
20.
Oncol Rep ; 43(3): 795-806, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020214

RESUMO

Establishing a prognostic genetic signature closely related to the tumor immune microenvironment (TIME) to predict clinical outcomes is necessary. Using the Gene Expression Omnibus (GEO) database of a non­small cell lung cancer (NSCLC) cohort and the immune score derived from the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, we applied the least absolute shrinkage and selection operator (LASSO) Cox regression model to screen a 10­gene signature among the 448 differentially expressed genes and found that the risk prediction models constructed by 10 genes could be more sensitive to prognosis than TNM (Tumor, Lymph node and Metastasis) stage (P=0.006). The CIBERSORT method was applied to quantify the relative levels of different immune cell types. It was found that the ratio of eosinophils, mast cells (MCs) resting and CD4 T cells memory activated in the low­risk group was higher than that in the high­risk group, and the difference was statistically significant (P=0.003, P=0.014 and P=0.018, respectively). Inconsistently, the ratio of resting natural killer (NK) cells and activated plasma cells in the low­risk group was significantly lower than that in the high­risk group (P=0.05 and P=0.009, respectively). Kaplan­Meier survival results showed that patients of the high­risk group had significantly shorter overall survival (OS) than those of the low­risk group in the training set (P<0.001). Furthermore, Kaplan­Meier survival showed that patients of the high­risk group had significantly shorter OS than those of the low­risk group (P=0.0025 and P=0.0157, respectively) in the validation set [GSE31210 and TCGA (The Cancer Genome Atlas)]. The 10­gene signature was found to be an independent risk factor for prognosis in univariate and multivariate Cox proportional hazard regression analyses (P<0.001). In addition, it was found that the risk model constructed by the 10­gene signature was related to the clinical related factors in logistic regression analysis. The genetic signature closely related to the immune microenvironment was found to be able to predict differences in the proportion of immune cells (eosinophils, resting MCs, memory activated CD4 T cells, resting NK cells and plasma cells) in the risk model. Our findings suggest that the genetic signature closely related to TIME could predict the prognosis of NSCLC patients, and provide some reference for immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Prognóstico , Microambiente Tumoral/imunologia , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Genéticas , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Estadiamento de Neoplasias , RNA Longo não Codificante/genética , Fatores de Risco , Transcriptoma/imunologia
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