{"title":"ITGB3 是一种新型预后生物标记物,与透明细胞肾细胞癌的甲基化异常和肿瘤免疫相关。","authors":"Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian","doi":"10.2174/0113862073311689240730112355","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.</p><p><strong>Methods: </strong>We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.</p><p><strong>Results: </strong>Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.</p><p><strong>Conclusion: </strong>Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.\",\"authors\":\"Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian\",\"doi\":\"10.2174/0113862073311689240730112355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.</p><p><strong>Methods: </strong>We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.</p><p><strong>Results: </strong>Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.</p><p><strong>Conclusion: </strong>Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.</p>\",\"PeriodicalId\":10491,\"journal\":{\"name\":\"Combinatorial chemistry & high throughput screening\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Combinatorial chemistry & high throughput screening\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0113862073311689240730112355\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073311689240730112355","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.
Background: Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.
Methods: We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.
Results: Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.
Conclusion: Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.
期刊介绍:
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.