CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma

Abstract

Background Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors. Methods HCCDB, CCLE, HPA and LinkedOmics online databases were used to explore the expression of CPNE1 gene and analyze the co-expression network of CPNE1 in hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis and regulators of CPNE1 networks in LIHC. HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and Hep3B cell was selected to construct CPNE1 overexpression cell line by transfection with plasmid. The effect of CPNE1 on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database and GSEA. Results CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. Knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. Overexpression of CPNE1 gene showed the opposite results. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (P < 0.001). GSEA results also showed that CPNE1 of LIHC was involved in some immune response regulating signaling pathways. Conclusions Our study firstly found the expression of CPNE1 was significantly higher in LIHC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. In addition, we identified the possible mechanism by which CPNE1 functioned in LIHC. CPNE1 influenced AKT/P53 pathway activation and LIHC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in LIHC.

Overexpression of Copines‐1 is associated with clinicopathological parameters and poor outcome in gastric cancer

“…In liver cancer, CPNE1 expression was significantly higher in liver hepatocellular carcinoma (LIHC) tissues than in matched normal liver tissues. Additionally, CPNE1 influenced the biological behaviors of LIHC cells and regulated AKT/P53 pathway activation in LIHC 28 . Collectively, these results support that CPNE1 may promote tumor development and progression.…”

“…Additionally, CPNE1 influenced the biological behaviors of LIHC cells and regulated AKT/P53 pathway activation in LIHC. 28 Collectively, these results support that CPNE1 may promote tumor development and progression.…”

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

“…CPNE1 has been indicated to regulate cell proliferation, migration and differentiation ( 15 , 16 ). Accumulating evidence reports that CPNE1 acts as an oncogene and is elevated in various malignancies, including lung cancer ( 17 ), gastric cancer ( 13 ), hepatocellular carcinoma ( 18 ) and colorectal cancer ( 19 ), but the biological function of CPNE1 in cancers remains unclear.…”

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

“…Tp53 is known as an important cell cycle regulator and a tumor suppressor. A previous study reported the abilities of CPNE1 to stimulate the proliferation and cell migration mediated by AKT/P53 signaling in liver cancer cells ( Su et al, 2022 ). E2F is a family of transcription factors that modulate the expression of genes involved in cellular proliferation and cell cycle ( Azechi et al, 2001 ).…”

“…In prostate cancer, CPNE1 proved to be a significant prognostic biomarker for evaluating recurrence-free survival, and was positively correlated with TRAF2 expression ( Liang et al, 2017 ). In liver cancer, knockdown of CPNE1 inhibited proliferation, migration and invasion via the AKT/P53 signaling ( Su et al, 2022 ). A recent study indicated that CPNE1 might serve as an independent prognostic biomarker for ccRCC by bioinformatics analysis and immunohistochemical staining ( Talaat et al, 2022 ).…”