Implication of COPB2 Expression on Cutaneous Squamous Cell Carcinoma Pathogenesis

SIMPLE SUMMARY: The present study aimed to evaluate the effect of COPB2 expression on cutaneous squamous cell carcinoma (cSCC) pathogenesis. cSCC, a common category of skin cancer, is marked by a reasonably favorable prognosis. However, there has been a steady rise in the annual incidence of cases; in particular, a subset of cases showed aggressive progression. However, the underlying molecular mechanism of cSCC pathogenesis is largely unknown. In the present study, we found that COPB2 may act as a potential oncogene and modulator of the tumor immune microenvironment in cSCC pathogenesis. Therefore, COPB2 can serve as a novel predictive prognostic biomarker and immunotherapeutic target in cSCC patients. ABSTRACT: The underlying molecular mechanisms of cutaneous squamous cell carcinoma (cSCC) pathogenesis are largely unknown. In the present study, we aimed to evaluate the effect of coatomer protein complex subunit beta 2 (COPB2) expression on cSCC pathogenesis. Clinicopathological significance of COPB2 in cSCC was investigated by analyzing the Gene Expression Omnibus (GEO) database and through a retrospective cohort study of 95 cSCC patients. The effect of COPB2 expression on the biological behavior of cSCC cells was investigated both in vitro and in vivo. We found that COPB2 expression was significantly higher in cSCC samples than in normal skin samples. In our cohort, a considerable association was found between COPB2 expression and indicators of tumor immune microenvironment (TIME), such as histocompatibility complex class (MHC) I, and MHC II, CD4+/ CD8+ tumor-infiltrating lymphocytes. Additionally, COPB2 expression had an independent impact on worsened recurrence-free survival in our cohort. Furthermore, decreased proliferation, invasion, tumorigenic activities, and increased apoptosis were observed after COPB2 knockdown in cSCC cells. COPB2 may act as a potential oncogene and candidate modulator of the TIME in cSCC. Therefore, it can serve as a novel predictive prognostic biomarker and candidate immunotherapeutic target in cSCC patients.