Arpit Kumar Pradhan1, Rudrarup Bose1, Shyamasree Ghosh1, Amitava Datta2
1School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Khurda, Odisha, India,
2School of Computer Scienceand Software Engineering, The University of Western Australia, Perth,WA 6009, Australia.
Introduction: Gallbladder cancer (GBC) is a fatal malignancy of gallbladder and bile ductswhich shows delayed symptoms and sometimes can be asymptomatic, being fatal. Reported globally, for a very low survival rate, it suffers from the lack of early diagnostic and prognostic markers. Single nucleotide polymorphisms (SNPs) have been reported to be associated in different cancers. Methods: In this study using in silico methods, we report for the first time a combination of SNPs from the coding and noncoding region leading to alteration in GBC. Different pipelines were designed for the study of SNPs. Regulatory role alteration of Synonymous and non-coding SNPs were studied using RegulomeDB, DeepSEA analysis and funcPred. Structural alteration and energy parameters for non-synonymous SNPs were studied by Swiss-PDB, Chimera and Gromacs. Protein stability analysis was done using MutPred, mCSM and I-mutant. Results: As a result, three potential variants from the coding region rs1042838, rs11887534, and rs700519 associated with progesterone receptor, ATP binding cassette subfamily G member 8 (ABCG8), and cytochrome P450 19A1, respectively, were predicted to be potentially damaging SNPs in GBC leading to structure and function alteration. Three noncoding SNPs (rs2978974, rs4633 and rs2830) and 1 missense SNP(rs523349) were shown to be associated with damaging effect in GBC, and one of these SNPs (rs2978974) showed significant chromatin feature alteration. Conclusion: Our study strongly shows that SNPs both in the coding and noncoding region may be exploited as a combination of potential biomarkers in early diagnosis of GBC due to structure function alteration by nonsynonymous SNPs and regulatory role alteration by noncoding SNPs.
Keywords: ABCG8, Cancer, Gallbladder cancer, Single‑nucleotide polymorphism.