A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival



Shen, Sipeng, Wei, Yongyue, Li, Yi, Duan, Weiwei, Dong, Xuesi, Lin, Lijuan, You, Dongfang, Tardon, Adonina, Chen, Chu, Field, John K ORCID: 0000-0003-3951-6365
et al (show 11 more authors) (2021) A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival. NPJ PRECISION ONCOLOGY, 5 (1). 39-.

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Abstract

The genetic architecture of non-small cell lung cancer (NSCLC) is relevant to smoking status. However, the genetic contribution of long-term smoking cessation to the prognosis of NSCLC patients remains largely unknown. We conducted a genome-wide association study primarily on the prognosis of 1299 NSCLC patients of long-term former smokers from independent discovery (n = 566) and validation (n = 733) sets, and used in-silico function prediction and multi-omics analysis to identify single nucleotide polymorphisms (SNPs) on prognostics with NSCLC. We further detected SNPs with at least moderate association strength on survival within each group of never, short-term former, long-term former, and current smokers, and compared their genetic similarity at the SNP, gene, expression quantitative trait loci (eQTL), enhancer, and pathway levels. We identified two SNPs, rs34211819<sub>TNS3</sub> at 7p12.3 (P = 3.90 × 10<sup>-9</sup>) and rs1143149<sub>SEPT7</sub> at 7p14.2 (P = 9.75 × 10<sup>-9</sup>), were significantly associated with survival of NSCLC patients who were long-term former smokers. Both SNPs had significant interaction effects with years of smoking cessation (rs34211819<sub>TNS3</sub>: P<sub>interaction</sub> = 8.0 × 10<sup>-4</sup>; rs1143149<sub>SEPT7</sub>: P<sub>interaction</sub> = 0.003). In addition, in silico function prediction and multi-omics analysis provided evidence that these QTLs were associated with survival. Moreover, comparison analysis found higher genetic similarity between long-term former smokers and never-smokers, compared to short-term former smokers or current smokers. Pathway enrichment analysis indicated a unique pattern among long-term former smokers that was related to immune pathways. This study provides important insights into the genetic architecture associated with long-term former smoking NSCLC.

Item Type: Article
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 26 Oct 2021 08:00
Last Modified: 18 Jan 2023 21:25
DOI: 10.1038/s41698-021-00182-3
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3141697

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