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

Haiting Zhou; Yi He; Yongbiao Huang; Rui Li; Hao Zhang; Xiaohui Xia; Huihua Xiong

doi:10.3389/fcell.2023.1157269

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

Front Cell Dev Biol. 2023 Apr 3:11:1157269. doi: 10.3389/fcell.2023.1157269. eCollection 2023.

Authors

Haiting Zhou¹, Yi He², Yongbiao Huang¹, Rui Li¹, Hao Zhang¹, Xiaohui Xia¹, Huihua Xiong¹

Affiliations

¹ Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
² Department of Orthopedics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Background: 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. Methods: In this study, we applied multiple bioinformatic databases to analyze the expression and clinical significance of CPNE1 in ccRCC. Co-expression analysis and functional enrichment analysis were investigated by LinkedOmics, cBioPortal and Metascape. The relationships between CPNE1 and tumor immunology were explored using ESTIMATE and CIBERSORT method. In vitro experiments, CCK-8, wound healing, transwell assays and western blotting were conducted to investigate the effects of gain- or loss-of-function of CPNE1 in ccRCC cells. Results: The expression of CPNE1 was notably elevated in ccRCC tissues and cells, and significantly correlated with grade, invasion range, stage and distant metastasis. Kaplan-Meier and Cox regression analysis displayed that CPNE1 expression was an independent prognostic factor for ccRCC patients. Functional enrichment analysis revealed that CPNE1 and its co-expressed genes mainly regulated cancer-related and immune-related pathways. Immune correlation 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 promoted proliferation, migration and invasion of ccRCC cells through EGFR/STAT3 pathway. 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 in ccRCC.

Keywords: CPNE1; EGFR/STAT3; immune infiltration; prognosis; renal cell carcinoma.

Grants and funding

This research was supported by the Chinese Society of Clinical Oncology Foundation of Hengrui Medicine (Grant No. Y-HR2020MS-1039) and Bethune Cancer Basic Research Program (Grant No. J202101E005).