Genetic Variants of CLEC4E and BIRC3 in Damage-Associated Molecular Patterns-Related Pathway Genes Predict Non-Small Cell Lung Cancer Survival.

dc.contributor.author

Liu, Lihua

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Liu, Hongliang

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Luo, Sheng

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Patz, Edward F

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Glass, Carolyn

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Su, Li

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Lin, Lijuan

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Christiani, David C

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Wei, Qingyi

dc.date.accessioned

2021-11-01T15:15:46Z

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2021-11-01T15:15:46Z

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2021

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2021-11-01T15:15:46Z

dc.description.abstract

Accumulating evidence supports a role of various damage-associated molecular patterns (DAMPs) in progression of lung cancer, but roles of genetic variants of the DAMPs-related pathway genes in lung cancer survival remain unknown. We investigated associations of 18,588 single-nucleotide polymorphisms (SNPs) in 195 DAMPs-related pathway genes with non-small cell lung cancer (NSCLC) survival in a subset of genotyping data for 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another independent subset of genotyping data for 984 patients from Harvard Lung Cancer Susceptibility Study. We performed multivariate Cox proportional hazards regression analysis, followed by expression quantitative trait loci (eQTL) analysis, Kaplan-Meier survival analysis and bioinformatics functional prediction. We identified that two SNPs (i.e., CLEC4E rs10841847 G>A and BIRC3 rs11225211 G>A) were independently associated with NSCLC overall survival, with adjusted allelic hazards ratios of 0.89 (95% confidence interval=0.82-0.95 and P=0.001) and 0.82 (0.73-0.91 and P=0.0003), respectively; so were their combined predictive alleles from discovery and replication datasets (P trend=0.0002 for overall survival). We also found that the CLEC4E rs10841847 A allele was associated with elevated mRNA expression levels in normal lymphoblastoid cells and whole blood cells, while the BIRC3 rs11225211 A allele was associated with increased mRNA expression levels in normal lung tissues. Collectively, these findings indicated that genetic variants of CLEC4E and BIRC3 in the DAMPs-related pathway genes were associated with NSCLC survival, likely by regulating the mRNA expression of the corresponding genes.

dc.identifier.issn

2234-943X

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2234-943X

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https://hdl.handle.net/10161/23956

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eng

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Frontiers Media SA

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Front Oncol

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10.3389/fonc.2021.717109

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damage-associated molecular pattern-related pathway

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non-small cell lung cancer

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single-nucleotide polymorphism

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survival

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variant

dc.title

Genetic Variants of CLEC4E and BIRC3 in Damage-Associated Molecular Patterns-Related Pathway Genes Predict Non-Small Cell Lung Cancer Survival.

dc.type

Journal article

duke.contributor.orcid

Luo, Sheng|0000-0003-4214-5809

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Patz, Edward F|0000-0003-3374-1596

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Glass, Carolyn|0000-0002-8850-9906

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Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

pubs.begin-page

717109

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School of Medicine

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Duke Cancer Institute

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Pharmacology & Cancer Biology

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Pathology

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Radiology, Cardiothoracic Imaging

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Duke

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Institutes and Centers

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Basic Science Departments

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Clinical Science Departments

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Radiology

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Duke Clinical Research Institute

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Biostatistics & Bioinformatics

pubs.publication-status

Published online

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11

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