Tumor Mutational Burden and Survival in Papillary Renal Cell Carcinoma Patients

Abstract

Background: Papillary renal cell carcinoma (PRCC) is the second most prevalent subtype of renal cell carcinoma (RCC), accounting for 15% of all RCCs. Tumor mutational burden (TMB) is a promising prognostic factor in many types of cancers. The present study aimed to investigate the association between TMB and patient survival in PRCC patients.Methods: Genomic and clinical data of 281 PRCC patients were collected from The Cancer Genome Atlas. Overall survival (OS) was compared between patients with high and low TMB using the Kaplan-Meier method with log-rank tests. Gene expression comparison and immune cell fraction comparison were performed using Student’s t test or Wilcoxon’s rank-sum test. Results: Patients with high TMB tumors had longer OS than those with low TMB tumors. Among tumor-infiltrating immune cells, high TMB tumors were associated with high levels of CD4+ T-cell infiltration, which were further associated with better survival. Furthermore, low TMB tumors were associated with a high level of infiltration of regulatory T-cells and dendritic cells. Among immune checkpoint genes, low TMB tumors expressed high levels of CD274, PDCD1LG2, LAG3, and TGFB1, and these genes were associated with a poor prognosis in PRCC. Among cytokine-related genes, low TMB tumors were associated with a high expression of IL6, whereas high TMB tumors were associated with a high expression of IFNA1.Conclusions: High TMB indicated better survival outcomes in PRCC patients. High TMB was associated with anti-tumor immune cell infiltration, whereas low TMB was associated with high expression of checkpoint genes that indicated a worse prognosis in RCC. Moreover, TMB was associated with the expression of immune cytokines. Thus, TMB may be a novel prognostic factor in PRCC.