The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma

Genes Genomics. 2020 Sep;42(9):1055-1066. doi: 10.1007/s13258-020-00974-0. Epub 2020 Jul 28.

Abstract

Background: TNFSF14 has been proven to play an important role in various types of tumors. However, its function in renal cell carcinoma (RCC) has not yet been fully elucidated.

Objective: In order to explore molecular mechanism of RCC, we evaluated the effect of TNFSF14 on RCC progression, prognosis and immune microenvironment.

Methods: Using TCGA database, the differential expression of TNFSF14 and its relationships between clinicopathological features and prognosis were determined. Cox univariate and multivariate analyses were successively performed to identify whether TNFSF14 was an independent prognostic factor. The discriminating ability of TNFSF14 in RCC prognosis analysis was validated under the same clinical subgroups. Tumor mutational burden (TMB) of each RCC samples was calculated and the differential expression of TNFSF14 between high- and low-TMB groups was analyzed. The immune abundances of 22 leukocyte subtypes in each RCC samples were presented through the CIBERSORT algorithm. TIMER database was used to explore the relationships between copy number of TNFSF14 and the infiltration levels of 6 immune cells.

Results: Overexpression of TNFSF14 implied adverse clinicopathological features and poor prognosis. Meanwhile, TNFSF14 was identified as an independent prognostic factor (HR = 1.047, P = 0.028) and possessed prevalent applicability in RCC prognostic analysis. TNFSF14 was upregulated in high-TMB group than that in low-TMB group (Log2FC = 0.722). Moreover, overexpression of TNFSF14 brought alteration of immune abundance of 8 leukocyte subtypes. Besides, somatic copy number alteration (SCNA) of TNFSF14 was associated with infiltration levels of 6 immune cells.

Conclusions: TNFSF14 has crucial impact on progression, prognosis and immune microenvironment in RCC. Besides, TNFSF14 may be a potential biomarker for predicting the efficacy and response rate of RCC immunotherapy.

Keywords: Clear cell renal cell carcinoma; Immunotherapy; Microenvironment; TCGA; TIMER; TNFSF14; Tumor mutation burden.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / pathology
  • Computational Biology / methods
  • Databases, Genetic
  • Humans
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Prognosis
  • Tumor Microenvironment / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism

Substances

  • Biomarkers, Tumor
  • TNFSF14 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 14