Evaluation of Cyclin-Dependent Kinase Inhibitor Signalling network in esophageal Adenocarcinoma Via computational and statistical approaches

Cyclin-dependent kinase inhibitor is a tumor suppressor gene which play essential role in cell cycle. Pervious work demonstrates that, mutation in CDKN2A gene cause uncontrolled proliferation, genomic stability, oncogenesis, and metastasis. To evaluate the role of CDKN2A signalling network in Esophageal adenocarcinoma we utilized cluster profiler, STRING database and cbioportal. Hypergeometric test was applied within R platform for the detection of biological function of CDKN2A and its interactor’s genes in the form of enrichmap including cnetplot and Dot plot. Possibility of four different oncogenic mutations (X153- splice/D153N) were observed on amino acid number 153 of CDKN2A genes among various samples. We reported that, TP53 is also highly mutated gene in Esophageal cancer, 87% cases associated with 180 TP53 mutations. In majority of cases, 15 R248Q/W mutations was observed at P53-DNA binding domain (95-288) of TP53. During network analysis, a solid association between CDKN2A and TP53 was observed while co-occurrence between CDKN2A and TP53 was detected in Esophageal adenocarcinoma during mutual exclusivity analysis (Log Odds Ratio= 1.521, p-value= 0.024, q-value=0.270). Our findings indicates that CDK6, MYC, CCND1, TP53 along with CDKN2A are very essential targets for multi-targeted therapy against Esophageal adenocarcinoma. Our research provide a new avenue to explore genomic features of CDKN2A and TP53 in Esophageal adenocarcinoma.