Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer

Objective Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism.Methods This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization.Results The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10.Conclusions Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer. CPNE1 accelerated the progression of ovarian cancer in vitro and in vivo , while the knockdown of CPNE1 led to opposite effects. Besides, a relationship between CPNE1 expression and macrophage infiltration was found and CPNE1 upregulated CD163 and CD206 to promote M2 macrophage polarization. Graphical Abstract

Automated summary

This study investigated the expression and function of CPNE1 in ovarian cancer. The results showed that CPNE1 overexpression was associated with poor prognosis in ovarian cancer and promoted tumor cell proliferation, invasion, and migration. Furthermore, CPNE1 was found to mediate M2 macrophage polarization and upregulate CD163, CD206, and interleukin-10, suggesting a potential therapeutic target for ovarian cancer.