Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12885-018-4471-x
Title: Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy
Authors: Limviphuvadh, V
Tan, C.S
Konishi, F
Jenjaroenpun, P
Xiang, J.S
Kremenska, Y
Mu, Y.S
Syn, N
Lee, S.C
Soo, R.A 
Eisenhaber, F 
Maurer-Stroh, S 
Yong, W.P 
Keywords: 5' nucleotidase
amino acid
gemcitabine
pyrimidine
antineoplastic agent
deoxycytidine
gemcitabine
tumor marker
adult
amino acid sequence
Article
blood toxicity
cancer patient
cohort analysis
controlled study
crystal structure
drug response
female
genotype
human
major clinical study
male
molecular mechanics
neutropenia
non small cell lung cancer
overall survival
protein dephosphorylation
protein function
protein protein interaction
pyrimidine metabolism
Singaporean
single nucleotide polymorphism
survival analysis
thrombocytopenia
treatment outcome
analogs and derivatives
clinical trial
epidemiology
genetics
genotyping technique
lung tumor
mortality
non small cell lung cancer
personalized medicine
procedures
Singapore
single nucleotide polymorphism
young adult
Adult
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung
Cohort Studies
Deoxycytidine
Female
Genotype
Genotyping Techniques
Humans
Lung Neoplasms
Male
Polymorphism, Single Nucleotide
Precision Medicine
Singapore
Survival Analysis
Treatment Outcome
Young Adult
Issue Date: 2018
Citation: Limviphuvadh, V, Tan, C.S, Konishi, F, Jenjaroenpun, P, Xiang, J.S, Kremenska, Y, Mu, Y.S, Syn, N, Lee, S.C, Soo, R.A, Eisenhaber, F, Maurer-Stroh, S, Yong, W.P (2018). Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy. BMC Cancer 18 (1) : 555. ScholarBank@NUS Repository. https://doi.org/10.1186/s12885-018-4471-x
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. © 2018 The Author(s).
Source Title: BMC Cancer
URI: https://scholarbank.nus.edu.sg/handle/10635/175384
ISSN: 1471-2407
DOI: 10.1186/s12885-018-4471-x
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