A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

Abstract

Given the importance of tripartite motif (TRIM) proteins in diverse cellular biological processes and that their dysregulation contributes to cancer progression, we constructed a robust TRIM family signature to stratify patients with kidney renal clear cell carcinoma (KIRC). Transcriptomic profiles and corresponding clinical information of KIRC patients were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. Prognosis-related TRIM family genes were screened and used to construct a novel TRIM family-based signature for the training cohort. The accuracy and generalizability of the prognostic signature were assessed in testing, entire, and external ICGC cohorts. We analyzed correlations among prognostic signatures, tumor immune microenvironment, and immune cell infiltration. The results of univariate Cox regression and Kaplan-Meier survival analyses revealed 27 TRIMs that were robustly associated with the prognosis of patients with KIRC. We applied Lasso regression and multivariate Cox regression analyses to develop a prognostic signature containing the TRIM1, 13, 35, 26, 55, 2, 47, and 27 genes to predict the survival of patients with KIRC. The accuracy and generalizability of this signature were confirmed in internal and external validation cohorts. We also constructed a predictive nomogram based on the signature and the clinicopathological characteristics of sex, age, and T and M status to aid clinical decision-making. We analyzed immune cell infiltration analysis and found that CD8 T cells, memory resting CD4 T cells, and M2 macrophages were the most enriched components in the KIRC tumor immune microenvironment. A higher level of immune infiltration by plasma cells, follicular helper T cells, and activated NK cells, and a lower level of immune infiltration by memory resting CD4 T cells, M1 and M2 macrophages, and resting dendritic cells were associated with higher risk scores. Overall, our eight-gene TRIM family signature has sufficient accuracy and generalizability for predicting the overall survival of patients with KIRC. Furthermore, this prognostic signature is associated with tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling

“…We recently developed a prognostic signature for clear cell renal cell carcinoma (ccRCC) using genes from the TRIM family. Additionally, we found that some TRIM proteins, such as TRIM26, had predictive value in ccRCC [ 36 ]. Nevertheless, the specific function of TRIM26 in ccRCC has not been previously documented.…”

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer

“…Thus lead to the diverse and even diametrically opposite cell function in cell proliferation and mitosis, immune response, tumorigenesis or harmonization of certain ubiquitination-related signal pathways [ 15 – 17 ]. Studies have verified that abnormal expression of TRIM family members were existed in multiple cancers [ 6 , 17 – 19 ], and effected the tumor cells by promoting epithelial mesenchymal transition (EMT) and aerobic glycolysis [ 20 ]. The TRIM family functioned in tumorigenesis based on their other non-classical domains.…”

A comprehensive analysis of the FOX family for predicting kidney renal clear cell carcinoma prognosis and the oncogenic role of FOXG1

“…A six hypoxia-related gene prognostic model was established to predict OS in patients with KIRC. Zheng et al [ 22 ]. Also established a similar prognostic model for KIRC patients via comprehensive analysis of tripartite motif (TRIM) proteins.…”