Expression Status of ABCC1, an ABC Transporter, as a Potential Biomarker of Disease-Free Survival and Chemotherapy Response in Colon Adenocarcinoma Patients.

Abstract

Introduction: The worldwide increasing incidence of colon adenocarcinoma (COAD) due to a lack of early diagnostic biomarkers and drug resistance makes it essential to identify new diagnostic, prognostic, and drug-resistance biomarkers of COAD. ABC transporters are the key players that confer resistance against chemotherapeutic drugs. This study was initiated to explore the diagnostic, prognostic, and therapeutic role of ABCC1 expression in COAD patients.

Methods: The cBioPortal database was used to extract the ABCC1 mutation data. Extensive bioinformatics tools were employed to predict the functional impact of mutations. UALCAN was employed to conduct ABCC1 expression, methylation, and overall survival analysis in COAD. Further, pan-cancer analysis was also performed by UALCAN. The correlation of ABCC1 methylation and mutations with overall survival was performed using the OncoDB database. The KM plotter was used for disease-free survival analysis of ABCC1. Meta-survival analysis was conducted using GENT2. The CCLE and GDSC databases were utilized for drug sensitivity analysis of ABCC1 expression in COAD and other cancers.

Results: Mutation analysis revealed that ABCC1 harbors damaging and pathogenic mutations in COAD with a frequency of 6%. The expression analysis showed the upregulation of ABCC1 at both transcriptomic and proteomic levels. The ABCC1 promoter was detected to be hypomethylated in COAD patients. Overall survival analysis of ABCC1 expression, methylation, and mutation level showed no significant association with survival in COAD patients. However, disease-free survival analysis showed a significant correlation with ABCC1 expression. Lastly, the drug sensitivity analysis depicted a significant association of ABCC1 expression with reduced drug sensitivity in various cancers.

Discussion: The high expression of ABCC1 suggested its role in COAD and highlighted its significance as a therapeutic target.

Conclusion: The findings suggested that ABCC1 can be employed as a diagnostic and therapeutic biomarker of COAD and can be used as an indicator of disease-free survival. However, no prognostic potential of ABCC1 in COAD was identified, predicting it as a poor prognostic biomarker of COAD.