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Abstract
Background To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer (ccRCC) and investigate the immune-associated genes by a comprehensive analysis of The Cancer Genome Atlas (TCGA) database. Methods We collected mRNA expression profiles of 537 ccRCC samples from the TCGA database. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. The differentially expressed genes (DEGs) were screened between high immune/stromal score and low immune/stromal score groups by the cutoff of |log (fold change)| > 1, P value <0.05 by using package “limma” in R. Functional enrichment analysis was performed by DAVID, and the protein-protein interaction network of intersected DEGs between stromal score and immune score groups was conducted using the STRING database. The Kaplan–Meier method was used to explore DEGs with predictive values in overall survival, and the prognostic DEGs were further validated in a Gene Expression Omnibus (GEO) dataset GSE29609. Results A higher immune score was associated with T3/4 (vs. T1/2, P < 0.001), N1 (vs. N0, P=0.05), M1 (vs. M0, P=0.004), G3/4 (vs. G1/2, P < 0.001), advanced AJCC stage (P < 0.001), and shorter overall survival (P=0.04). Intersected DEGs between immune and stromal score groups were 48 upregulated and 47 downregulated genes, with 43 DEGs associated with overall survival in ccRCC. After validation by a cohort of 39 ccRCC cases with detailed follow-up information from GSE29609, six immune-associated DEGs including CASP5, HSD11B1, VSIG4, HMGCS2, HSD11B2, and OGDHL were demonstrated to be predictive of prognosis in ccRCC. Conclusions Our study elucidated tight associations between immune score and clinical characteristics as well as prognosis in ccRCC. Moreover, six DEGs were explored and validated to exert predictive values in overall survival of ccRCC.
Highlights
To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer and investigate the immune-associated genes by a comprehensive analysis of e Cancer Genome Atlas (TCGA) database
A total of 537 clear cell renal cell cancer (ccRCC) patients with gene expression profiles and clinical information were collected from the TCGA database. e patients were diagnosed as ccRCC between 1998 and 2013
According to the ESTIMATE algorithm, immune scores were distributed between − 693.96 and 3328.21, while stromal scores ranged from − 1433.77 to 1411.35
Summary
To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer (ccRCC) and investigate the immune-associated genes by a comprehensive analysis of e Cancer Genome Atlas (TCGA) database. E Kaplan–Meier method was used to explore DEGs with predictive values in overall survival, and the prognostic DEGs were further validated in a Gene Expression Omnibus (GEO) dataset GSE29609. Intersected DEGs between immune and stromal score groups were 48 upregulated and 47 downregulated genes, with 43 DEGs associated with overall survival in ccRCC. After validation by a cohort of 39 ccRCC cases with detailed follow-up information from GSE29609, six immune-associated DEGs including CASP5, HSD11B1, VSIG4, HMGCS2, HSD11B2, and OGDHL were demonstrated to be predictive of prognosis in ccRCC.
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