CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment

Abstract

Little is known about the oncogenic role or biological function of copine Ⅷ (CPNE8) in gastric cancer (GC). Based on TCGA database, we screened for CPNE8 and analyzed the expression of CPNE8 in GC. The correlations between CPNE8 and clinical features were analyzed using TCGA and GEO databases. The prognostic value of CPNE8 was assessed using Cox analysis and Kaplan-Meier curves. The results showed that increased expression of CPNE8 was positively correlated with metastasis and can be considered an independent prognostic risk factor for poor survival. We found that CPNE8 can promote cell proliferation, migration, and invasiveness in GC using in vitro and in vivo experiments. Our study demonstrated that CPNE8 promotes tumor progression via regulation of focal adhesion, and these effects can be rescued by focal adhesion kinase ( FAK ) inhibitor GSK2256098 or knockdown of FAK . In addition, CPNE8 was correlated significantly with the infiltration of cancer-associated fibroblasts and immune cells, as demonstrated by various algorithms, and high CPNE8 expression predicted poor efficacy of immune checkpoint therapy. Our findings suggest that CPNE8 modulates focal adhesion and tumor microenvironment to promote GC progression and invasiveness and could serve as a novel prognostic biomarker in GC.

Molecular subtype construction and prognosis model for stomach adenocarcinoma characterized by metabolism-related genes

“…In breast cancer, glucose metabolism levels could be promoted by stabilizing p53-induced SERPINE1 in the miR-1185-2-3p-GOLPH3L pathway [ 42 ]. Enhanced CPNE8 expression samples was related to clinical characteristics and was predictive of unfavorable survival of patients with gastric cancer [ 43 ]. Those data supported the reliability of the current prognostic model developed using the four genes.…”

Correlation analysis of disulfidptosis-related gene signatures with clinical prognosis and immunotherapy response in sarcoma

“…Focal adhesion is crucial in the invasiveness and metastasis of tumors. Zhang et al 19 observed the involvement of CPNE8 in regulating focal adhesion and TME to improve progression and invasiveness in gastric cancer, indicating its potential as a novel prognostic biomarker. Collagen is the principal structural protein and a vital constituent of the ECM, possessing paramount importance.…”

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“…The GO enrichment analysis showed that dysregulated circRNAs significantly impact cell growth, proliferation, apoptosis, differentiation, survival, motility, and metabolism, which are crucial in the tumorigenesis and development of osteosarcoma. The results of the KEGG pathway analysis identified several important signaling pathways, including focal adhesion, which plays a critical role in cell migration, invasion, and angiogenesis during cancer progression [ 34 , 35 ]. The FoxO signaling pathway is involved in key cellular processes in cancer, such as cell differentiation, proliferation, apoptosis, DNA damage, and repair [ 36 ].…”