Integrative characterization and validation of tumor-associated immune signature combined with immune-infiltration analysis in clear cell renal cell carcinoma

Abstract

Background We aimed to explore and validate a prognostic immune signature for predicting the prognosis of ccRCC patients, combined with immune-infiltration analysis. Methods We obtained the multi-omics data from public datasets. Differential analysis was performed by edgeR package. Prognostic immune signature was identified by univariate Cox analysis, and we constructed an integrative tumor-associated immune Genes (TAIG) model from the multivariate Cox results. Functional analysis was conducted to uncover the related crosstalk. Importantly, we implemented the CIBERSORT algorithm to estimate the immune cell fractions in ccRCC samples and analyzed the differential abundance of tumor-infiltrating immune cells in two TAIG groups using Wilcoxon rank-sum test. The prognostic role of differential immune cells was further assessed by Kaplan-Meier analysis. In addition, we investigated the associations of single immune signature with specific immune cells. Results A total of 628 ccRCC patients were included in our integrative analysis, including 537 ccRCC patients in discovery group and 91 patients in validation group. Then, we identified the 14 key immune signatures. The AUC was 0.802 and patients with higher TAIG suffered from worse prognosis. Correlation analysis indicated that TAIG correlated tightly with clinical variables and TMB. Moreover, functional analysis also implicated the immune-related GO items or crosstalk. Therefore, we discovered the relationships of TAIG with tumor-infiltrating immune cells. The differential abundance of immune cells showed significant prognostic difference consisted of memory activated CD4 + T cell, T follicular helper cells, T regulatory cell, and so on. Moreover, we also characterized the associations between identified signature with specific immune cells. Finally, the 5-year AUC in ICGC cohort was 0.72, suggesting the robustness of TAIG that we constructed. Conclusions Totally, our team characterized the tumor-associated immune signature in ccRCC and further uncovered the prognostic tumor-infiltrating immune cells related with TAIG, providing a comprehensive foundation for investigating mechanisms or individualized immunotherapy.