Dataset Information

Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment.

ABSTRACT: Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in clear cell renal cell carcinoma (ccRCC). This study categorized ccRCC cases into high and low score groups based on their immune/stromal scores generated by the ESTIMATE algorithm, and identified an association between these scores and prognosis. Differentially expressed tumor environment (TME)-related genes extracted from common upregulated components in immune and stromal scores were described using functional annotations and protein-protein interaction (PPI) networks. Most PPIs were selected for further prognostic investigation. Many additional previously neglected signatures, including AGPAT9, AQP7, HMGCS2, KLF15, MLXIPL, PPARGC1A, exhibited significant prognostic potential. In addition, multivariate Cox analysis indicated that MIXIPL and PPARGC1A were the most significant prognostic signatures, and were closely related to immune infiltration in TCGA cohort. External prognostic validation of MIXIPL and PPARGC1A was undertaken in 380 ccRCC cases from a real-world cohort. These findings indicate the relevance of monitoring and manipulation of the microenvironment for ccRCC prognosis and precision immunotherapy.

SUBMITTER: Xu WH

PROVIDER: S-EPMC6756904 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment.

Xu Wen-Hao WH Xu Yue Y Wang Jun J Wan Fang-Ning FN Wang Hong-Kai HK Cao Da-Long DL Shi Guo-Hai GH Qu Yuan-Yuan YY Zhang Hai-Liang HL Ye Ding-Wei DW

Aging 20190907 17

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in clear cell renal cell carcinoma (ccRCC). This study categorized ccRCC cases into high and low score groups based on their immune/stromal scores generated by the ESTIMATE algorithm, and identified an association between these scores and prognosis. Differentially expressed tumor environment (TME)-related genes extracted from common upregulated components in immune and stromal ...[more]

PMID: 31493764

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Project description:Background: Although DBT is strongly associated with human tumorigenesis and progression through a variety of pathways, the role of DBT in clear cell renal cell carcinoma (ccRCC) has not been well established. Materials and methods: The Cancer Genome Atlas (TCGA)-Kidney renal clear cell carcinoma (KIRC) databset provides RNA sequencing data and clinicopathological information on ccRCC. The Gene Expression Omnibus (GEO) database was used to validate the DBT expression levels, and qPCR was used to examine the DBT expression in renal cancer cell lines and ccRCC tissue samples from our centre. In parallel, DBT protein expression was explored in the Human Protein Atlas (HPA) database, and western blotting and immunohistochemistry of renal cancer cell lines and ccRCC tissues validated the results. Additionally, the diagnostic and prognostic value of DBT was comprehensively evaluated by receiver operating characteristic (ROC) curves, univariate and multivariate Cox regression analyses, and Kaplan‒Meier survival analysis. The protein‒protein interaction (PPI) network based on the STRING website, Gene Ontology (GO) analysis, Kyoto Gene and Genome Encyclopedia (KEGG) analysis and gene set enrichment analysis (GSEA) further provided a landscape of the molecular mechanisms of DBT in ccRCC. Finally, the TIMER 2.0, GEPIA and TISIDB websites were used to understand the relationship between DBT and immune characteristics. Results: The mRNA expression and protein expression of DBT were significantly downregulated in ccRCC tissues relative to normal tissues, which was associated with poor clinical outcomes. DBT has an encouraging discriminatory power for ccRCC and is an independent prognostic factor for ccRCC patients. Mechanistically, DBT is mainly involved in the regulation of immune-related signalling pathways in ccRCC; it is associated with a variety of immune infiltrating cells and immune checkpoints. Conclusion: DBT is a tumour suppressor gene in ccRCC and could be used as a new biomarker for diagnostic and prognostic purposes, and it is associated with immune infiltration in ccRCC.

Dataset Information

Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment.

Publications

Prognostic value and immune infiltration of novel signatures in clear cell renal cell carcinoma microenvironment.

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