Integrated Analysis of the Oncogenic Value of CPNE1 and CPNE3 in Non-Small Cell Lung Cancer

Abstract Background Copines (CPNEs) are calcium-dependent, soluble and ubiquitous proteins found in eukaryotic organisms and protists. Recent evidence has also highlighted the roles of these protein play in regulating cancer immune responses and development. However, the specific expression, distribution and roles of CPNEs in NSCLC are poorly studied. Methods GSE and GEPIA2 database were selected to explore the expression levels of CPNEs in lung cancer tissues, which were verified by qRT-PCR analysis. The Kaplan-Meier plotter and GEPIA database were used to assess the effect of CPNE expression on patient survival. cBioportal database was used for genetic mutation analysis. FunRich database were used to predict the potential biological pathway. Finally, ssGSEA database was performed for immune infiltration analysis. Results Among all CPNEs, high expression of CPNE1 and CPNE3 were valuable for predicting both OS and DFS in lung cancer patients, which were associated with advanced TNM stages, lymph node metastasis and drug resistance to EGFR-TKIs. However, no statistical significance between CPNEs and the efficiency to immunotherapy was observed, which was further validated by weak correlation between CPNEs expression and immune cell infiltration levels. The processes of regulation of nucleobase and nucleotide, signal transduction, cell metabolism were involved in the effect of CPNE1 and CPNE3 on tumor pathogenesis. In terms of biological pathways, TGF-beta pathway, PI3K/AKT pathway, mTOR pathway and EGFR signaling pathway were most relevant to CPNE1 and CPNE3. Conclusions We highlighted the protumor role of CPNE1 and CPNE3 among all CPNEs, which may provide important therapeutic targets for lung cancer.