AUTHOR=Zhou Haiting , He Yi , Huang Yongbiao , Li Rui , Zhang Hao , Xia Xiaohui , Xiong Huihua 

TITLE=Comprehensive analysis of prognostic value, immune implication and biological function of CPNE1 in clear cell renal cell carcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1157269

DOI=10.3389/fcell.2023.1157269

ISSN=2296-634X

ABSTRACT=Elevated expression of Copine-1 (CPNE1) has been proved in various cancers; however, the underlying mechanisms by which it affects clear cell renal cell carcinoma (ccRCC) are unclear. In this study, through a series of bioinformatic analyses, we found that CPNE1 was notably elevated in ccRCC tissues, and high expression of CPNE1 associated with more aggressive clinic features and poor prognosis. Moreover, the multivariate prognostic analysis showed that CPNE1 was an independent prognostic factor associated with ccRCC. Functional enrichment analyses also revealed that CPNE1 and its co-expressed genes mainly regulated cancer-related and immune-related pathways. Immune analysis showed that CPNE1 expression was significantly related to immune and estimate scores. CPNE1 expression was positively related to higher infiltrations of immune cells, such as CD8+ T cells, plasma cells and regulatory T cells, exhibited lower infiltrations of neutrophils. Meanwhile, elevated expression of CPNE1 was characterized by high immune infiltration levels, increased expression levels of CD8+ T cell exhaustion markers (CTLA4, PDCD1 and LAG3) and worse response to immunotherapy. In vitro functional studies demonstrated that CPNE1 silencing inhibited the proliferation, migration and invasion of ccRCC cells. Mechanistically, loss of CPNE1 decreased the phosphorylation level of EGFR and STAT3. Overexpression of CPNE1 gene showed the opposite results. In conclusion, CPNE1 is a reliable clinical predictor for the prognosis of ccRCC and promotes proliferation and migration by activating EGFR/STAT3 signaling. Moreover, CPNE1 significantly correlates with immune infiltration and immunotherapy responses in ccRCC.