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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Cancer 1/2018

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

Zeitschrift:
BMC Cancer > Ausgabe 1/2018
Autoren:
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
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12885-018-4471-x) contains supplementary material, which is available to authorized users.

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’.
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