Identification of an immune-related risk signature for predicting prognosis in clear cell renal cell carcinoma

Abstract

Immune status affects the initiation and progression of clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma. In this study, we identified an immune-related, five-gene signature that improves survival prediction in ccRCC. Patients were classified as high-and low-risk based on the signature risk score. Survival analysis showed differential prognosis, while principal component analysis revealed distinctly different immune phenotypes between the two risk groups. High-risk patients tended to have advanced stage, higher grade disease, and poorer prognoses. Functional enrichment analysis showed that the signature genes were mainly involved in the cytokine-cytokine receptor interaction pathway. Moreover, we found that tumors from high-risk patients had higher relative abundance of T follicular helper cells, regulatory T cells, and M0 macrophages, and higher expression of PD-1, CTLA-4, LAG3, and CD47 than low-risk patients. This suggests our gene signature may not only serve as an indicator of tumor immune status, but may be a promising tool to select high-risk patients who may benefit from immune checkpoint inhibitor therapy. Multivariate Cox regression analysis showed that the signature remained an independent prognostic factor after adjusting for clinicopathological variables, while prognostic accuracy was further improved after integrating clinical parameters into the analysis.

A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma

“…Moreover, the gene annotation and analysis results revealed that overexpressed genes in the high-risk patients are involved in incretin synthesis, secretion, and inactivation, and that the down-regulated genes participate in complement and coagulation cascades, metabolism of xenobiotics by cytochrome P450, response to glucose. Hua et al 17 identified an immune-related risk signature for predicting prognosis of ccRCC, they found that tumors from high-risk patients had higher relative abundance of T follicular helper cells, regulatory T cells than low-risk patients. Moreover, the time-dependent ROC analysis revealed that the AUC was 0.753, 0.686, and 0.637 at 1, 3, and 5 years.…”

“…Hua et al . 17 identified an immune-related risk signature for predicting prognosis of ccRCC, they found that tumors from high-risk patients had higher relative abundance of T follicular helper cells, regulatory T cells than low-risk patients. Moreover, the time-dependent ROC analysis revealed that the AUC was 0.753, 0.686, and 0.637 at 1, 3, and 5 years.…”

A Meta-Analysis of Glasgow Prognostic Score and Modified Glasgow Prognostic Score as Biomarkers for Predicting Survival Outcome in Renal Cell Carcinoma

“…At present, the number of studies revealing the correlation between GPS/mGPS and the survival outcome of RCC is increasing, and the results indicate the prognostic value of GPS/mGPS (15)(16)(17)(18)(19)(20). Controversially, several recent systematic reviews and meta-analyses have provided increasing evidence, but the results remain inconclusive.…”

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape

“…e ROC analysis showed that our signature had an accurate prognostic performance. Additionally, compared with several existing signatures for the TCGA discovery cohorts, our IRGs signature was demonstrated to have a superior predictive accuracy for 5-year survival (AUC � 0.688 vs. 0.637 [32]/ 0.649 [33]/0.660 [34]). We also performed Kaplan-Meier analysis in stratified cohorts and found its ability to identify patients with worse survival regardless of other clinical variables.…”