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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy

Authors: Vachiranee Limviphuvadh, Chee Seng Tan, Fumikazu Konishi, Piroon Jenjaroenpun, Joy Shengnan Xiang, Yuliya Kremenska, Yar Soe Mu, Nicholas Syn, Soo Chin Lee, Ross A. Soo, Frank Eisenhaber, Sebastian Maurer-Stroh, Wei Peng Yong

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients.

Methods

Using a pathway approach that incorporates comprehensive protein-protein interaction data to systematically extend the gemcitabine pharmacologic pathway, we identified 77 related nsSNPs, common in the Singaporean population. After that, we used five computational criteria to prioritize the SNPs based on their importance for protein function. We specifically selected and screened six candidate SNPs in a patient cohort with NSCLC treated with gemcitabine-based chemotherapy.

Result

We performed survival analysis followed by hematologic toxicity analyses and found that three of six candidate SNPs are significantly correlated with the patient outcome (P < 0.05) i.e. ABCG2 Q141K (rs2231142), SLC29A3 S158F (rs780668) and POLR2A N764K (rs2228130).

Conclusions

Our computational SNP candidate enrichment workflow approach was able to identify several high confidence biomarkers predictive for personalized drug treatment outcome while providing a rationale for a molecular mechanism of the SNP effect.

Trial registration

NCT00695994. Registered 10 June, 2008 ‘retrospectively registered’.
Appendix
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Metadata
Title
Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy
Authors
Vachiranee Limviphuvadh
Chee Seng Tan
Fumikazu Konishi
Piroon Jenjaroenpun
Joy Shengnan Xiang
Yuliya Kremenska
Yar Soe Mu
Nicholas Syn
Soo Chin Lee
Ross A. Soo
Frank Eisenhaber
Sebastian Maurer-Stroh
Wei Peng Yong
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4471-x

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