Toll-like receptor 2 (TLR2) is a candidate prognostic factor in testicular germ cell tumors as well as an indicator of immune function in the tumor microenvironment

Bioengineered. 2021 Dec;12(1):1939-1951. doi: 10.1080/21655979.2021.1927560.

Abstract

Testicular cancer is the most common malignant tumor in young men, and its incidence has increased in recent years. The tumor microenvironment (TME) plays a crucial role in the development and progression of tumors; however, the TME of testicular germ cell tumor (TGCT) is poorly understood. In this study, we downloaded information for 156 TGCT cases from The Cancer Genome Atlas (TCGA) database, used the ESTIMATE method to determine immune and stromal scores, and used CIBERSORT to calculate the proportion of tumor-infiltrating immune cells (TICs). The differentially expressed genes were subjected to a COX regression analysis and used for the construction of a protein-protein interaction (PPI) network. Toll-like receptor 2 (TLR2) was identified as a predictive marker by combining the results of the Cox regression analysis and PPI network. A survival analysis showed that TLR2 was positively correlated with TGCT survival. A gene set enrichment analysis indicated that genes in the high TLR2 expression group were enriched for cell adhesion molecules (CAMs) and the chemokine signaling pathway, and genes in the low TLR2 expression group were mainly enriched in the spliceosome. Regarding proportions of TICs, naive B cells and follicular helper T cells were negatively correlated with the expression of TLR2. This suggests that as TLR2 expression increases, the immunocompetence of the TME decreases. The expression of TLR2 may affect the prognosis of TGCT, suggesting that this locus can be used as a prognostic factor for TGCT.

Keywords: TCGA; TLR2; Tumor microenvironment; testicular germ cell tumors; tumor-infiltrating immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Databases, Genetic
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Neoplasms, Germ Cell and Embryonal* / diagnosis
  • Neoplasms, Germ Cell and Embryonal* / genetics
  • Neoplasms, Germ Cell and Embryonal* / immunology
  • Neoplasms, Germ Cell and Embryonal* / mortality
  • Prognosis
  • Testicular Neoplasms* / diagnosis
  • Testicular Neoplasms* / genetics
  • Testicular Neoplasms* / immunology
  • Testicular Neoplasms* / mortality
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 2 / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • TLR2 protein, human
  • Toll-Like Receptor 2

Supplementary concepts

  • Testicular Germ Cell Tumor

Grants and funding

This study was supported by National Science Foundation [No. 81902565],funding from Young Talent Development Plan of Changzhou Health Commission (No. CZQM2020065), Changzhou Sci & Tech program (CJ20190100), Young Scientists Foundation of Changzhou No.2 People’s Hospital (YJRC202039; 2019K008). Hospital-level discipline funding (YJXK202013), Innovation Team funding (XK201803), Top Talent Project (RC201620).