Abstract
Background: Vasculogenic mimicry (VM) is correlated with higher tumor grade, cancer cell metastasis and invasion, and poorer prognosis in lung cancer patients. CPNE3 reportedly acts as an oncogene to promote tumorigenesis. However, whether CPNE3 regulates VM in NSCLC remained largely unknown. Methods: In the present study, TCGA database and GEPIA2 web server were selected to explore CPNE3 expression in lung cancer tissues, which was verified via qRT-PCR analysis. The Kaplan-Meier plotter and PrognoScan web servers were used to assess the effect of CPNE3 expression on patient survival. The cBioPortal platform was used for genetic mutation analysis. Transwell assay, three-dimensional culture and western blot were used to confirm the role and mechanism of CPNE3 in mediating VM and cell metastasis. Finally, ssGSEA and TISIDB were applied for immune infiltration analysis. Results: We found that among all CPNEs, high expression of CPNE3 was valuable for predicting OS in lung cancer patients, and was associated with advanced TNM stages. Missense substitution partially led to the expression alteration of CPNE3 gene. CPNE3 can promote VM formation and cell metastasis via EMT process. However, a weak correlation was found between CPNE3 expression and immune cell infiltration levels. Conclusions: CPNE3 regulates tumor cell migration, invasion, VM formation and immune evasion by acting as an oncogene in NSCLC, implying that CPNE3 can serve as a potential anti-angiogenesis target for NSCLC.