Year : 2018  |  Volume : 9  |  Issue : 2  |  Page : 137-149

An In silico method to study structure, function, and regulatory role alteration mediated by single-nucleotide polymorphisms in gallbladder cancer

1 School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Khurda, Odisha, India
2 School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA 6009, Australia

Correspondence Address:
Arpit Kumar Pradhan
School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Bhimpur-Padanpur, Jatni, Khurda - 752 050, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jnsbm.JNSBM_233_17

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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.

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