BACKGROUND
Worldwide increasing incident of colorectal adenocarcinoma (COAD) and development of resistance against chemotherapeutic drugs is a big challenge in recent era for researcher and health professional.
OBJECTIVE
This study was aimed to identify new biomarkers for early diagnosis, treatment and to overcome drug resistant in COAD patient. ABC transporter genes are key player in the development of resistance against chemotherapeutic drugs. Therefore, we initiate a study to explore the role of ABCC1 transporter by analyzing its mutatome, expression variations, promoter methylation level, clinical outcome, and drug sensitivity analysis in COAD patients
METHODS
We use cBioPortal and UALCAN to retrieve data regarding ABCC1 expression and its promoter methylation. KM plotter was used to retrieve data to study impact on survival of patient, and CCLE GDSC toolkit database was used for analysis of effect of ABCC1 overexpression on tumor’s response to various drugs.
RESULTS
Mutatome analysis show that in COAD patient ABCC1 was 2.2% mutated and most of frequent noted mutations were missense that are thought to be involved in up-regulation of ABCC1 transporter expression and may cause drug resistance. Data analysis from UALCAN showed that ABBC1 expression was high in COAD patients with various clinicopathological features than normal controls. Kaplan Meier survival analysis of ABCC1 show that overexpression decrease overall survival rate of the COAD patients.
CONCLUSIONS
Ultimately, the overexpression of ABCC1 was found decreasing the sensitivity of various important chemotherapeutic drugs in COAD patient via CCLE GDSC toolkit database analysis. By controlling overexpression of ABCC1, drug resistance can be overcome and effectiveness of various drugs can be increased in COAD patient