Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer

Abstract

The present study sought to investigate the correlation between CAAP1 and platinum resistance in ovarian cancer and to preliminarily explore the potential biological function of CAAP1. Proteomic analysis was used to analyze differentially expressed proteins in platinum-sensitive and -resistant tissue samples of ovarian cancer. The Kaplan-Meier plotter was used for prognostic analysis. Immunohistochemistry assay and chi-square test were employed to explore the relationship between CAAP1 and platinum resistance in tissue samples. Lentivirus transfection, immunoprecipitation-mass spectrometry, and bioinformatics analysis were used to determine the potential biological function of CAAP1. Based on results, the expression level of CAAP1 was significantly higher in platinum-sensitive tissues compared to that in resistant tissues. Chi-square test demonstrated that there is a negative correlation between high expression of CAAP1 and platinum resistance. Overexpression of CAAP1 increased cis‑platinum sensitivity of the A2780/DDP cell line likely via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. In summary, there is a negative correlation between high expression of CAAP1 and platinum resistance. CAAP1 might be a potential biomarker for platinum resistance in ovarian cancer. SIGNIFICANCE: Platinum resistance is a key factor affecting the survival of ovarian cancer patients. Understanding the mechanisms of platinum resistance is highly important for ovarian cancer management. Here, we performed the DIA- and DDA-based proteomics to analyze differentially expressed proteins in tissue and cell samples of ovarian cancer. We found that the protein identified as CAAP1, which was first reported to be involved in the regulation of apoptosis, may be negatively correlates with platinum resistance in ovarian cancer. In addition, we also found that CAAP1 enhanced the sensitivity of platinum-resistant cells to cis‑platinum via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. Our data would be useful to reveal novel molecular mechanisms of platinum resistance in ovarian cancer.

Keywords: CAAP1; Ovarian cancer; Platinum resistance; Potential biomarkers; Proteomic analysis.