GABRP is a potential chemoresistance regulator in colorectal cancer

Abstract

Abstract Background: Colorectal cancer (CRC) is one of the cancers with high morbidity and mortality worldwide. Chemotherapy is commonly used for metastatic or more advanced CRC. The mechanism of CRC chemoresistance is still under active investigation. Therefore, we identify and validate differentially expressed genes (DEGs) between oxaliplatin/5-FU resistant and sensitive cells.Methods and Results: Three datasets of colorectal cancer patients (GSE28691, GSE81006, and GSE77932) from Gene Expression Omnibus (GEO) database were analyzed and volcano plots for DEGs were generated using GEO2R tool. The intersection of three GEO datasets showed that GABRP was significantly upregulated in chemo-resistant CRC cells or patients with an adjusted p-value less than 0.01. The STRING website analyzed the potential protein-protein interaction (PPI) network with GABRP. The PPI network predicted ANKRD66, CLINT1, HAP1, PLCL1, GABARPAP, GABARAPL1, NSF, GABARAPL2, TRAK2, and CLIC3 had a high likelihood to interact with GABRP. Especially, GABARAP, GABARAPL1, ANKRD66, CLINT1, and CLIC3 were enriched as the most possible associated protein with GABRP among the networks. GABRP was significantly highly expressed in both oxaliplatin/5-FU resistant CRC cells than in those counterparts sensitive CRC cells using quantitative PCR (qPCR) analysis. Consistently, TCGA and oncomine database confirmed that high expression of GABRP in various cancer patients including CRC patients tends to have relatively lower survival and disease-free survival rate.Conclusion: We identify GABRP as a promising drug target to mediate oxaliplatin or 5-FU resistance in CRC. It provided the theoretical basis and potential clinical value for CRC patients.