CD112 is an epithelial-to-mesenchymal transition-related and immunological biomarker in pan-cancer.

Abstract

The nectin adhesion molecule CD112, an important component of tumor progression, belongs to the nectin family. However, a comprehensive evaluation of its clinical relevance and mechanism in various cancers is yet to be conducted. This investigation fully examined the relationship between prognosis and CD112 expression. We clarified the function of CD112 in tumor immunity by employing The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. This involved examining its connections to tumor mutation burden (TMB), DNA methylation, tumor immune invasion, mismatch repair (MMR), microsatellite instability (MSI), and common immune checkpoint inhibitors (ICIs). Additionally, the impact of CD112 knockdown on cell function was examined in colorectal cancer (CRC) cell lines. In the current study, we found malignant tissues express high levels of CD112, which was related to TMB, MMR, MSI, and DNA methylation. Survival analysis indicated that patients with high CD112 expression had an unfavorable prognosis more frequently. In addition, CD112 expression was negatively associated with infiltration levels of CD4 positive (CD4+) T cells, CD8 positive (CD8+) T cells, and T cells. Western blotting and pathway enrichment analysis showed that CD112 is significantly linked to epithelial-to-mesenchymal transition (EMT). Additionally, CRC cells migrate and proliferate less when CD112 was knocked down. CD112 expression was found to be negatively associated with anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) treatment outcomes in patients. CD112 may act as a possible prognostic marker in immune therapy and may stimulate tumor growth by upregulating the EMT pathway.