Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study

Abstract Background and Objective To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods “Blood +” high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics da...

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Main Authors: Yutong Wu, Huiwen Xu, Liping Mao, Rongrong Zhao, Junfeng Chu, Lili Huang, Wendi Zhang, Yiran Liu, Qiong Chen, Xiaobo Tao, Siqi Li, Shenxuan Zhou, Anhui Ning, Zhenyu Li, Tian Tian, Lei Zhang, Jiahua Cui, Guangyu Tian, Minjie Chu
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70247
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author Yutong Wu
Huiwen Xu
Liping Mao
Rongrong Zhao
Junfeng Chu
Lili Huang
Wendi Zhang
Yiran Liu
Qiong Chen
Xiaobo Tao
Siqi Li
Shenxuan Zhou
Anhui Ning
Zhenyu Li
Tian Tian
Lei Zhang
Jiahua Cui
Guangyu Tian
Minjie Chu
author_facet Yutong Wu
Huiwen Xu
Liping Mao
Rongrong Zhao
Junfeng Chu
Lili Huang
Wendi Zhang
Yiran Liu
Qiong Chen
Xiaobo Tao
Siqi Li
Shenxuan Zhou
Anhui Ning
Zhenyu Li
Tian Tian
Lei Zhang
Jiahua Cui
Guangyu Tian
Minjie Chu
author_sort Yutong Wu
collection DOAJ
description Abstract Background and Objective To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods “Blood +” high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non‐tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL‐SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL‐SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. Results A total of 7 pQTL‐SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL‐SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL‐SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. Conclusion A total of 4 pQTL‐SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.
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spelling doaj-art-50b80b0c7f4a4d51a67d2c51dc34c3d02025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70247Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage studyYutong Wu0Huiwen Xu1Liping Mao2Rongrong Zhao3Junfeng Chu4Lili Huang5Wendi Zhang6Yiran Liu7Qiong Chen8Xiaobo Tao9Siqi Li10Shenxuan Zhou11Anhui Ning12Zhenyu Li13Tian Tian14Lei Zhang15Jiahua Cui16Guangyu Tian17Minjie Chu18Department of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Oncology Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) Nantong Jiangsu ChinaDepartment of Oncology Jiangdu People's Hospital of Yangzhou Yangzhou ChinaDepartment of Oncology Jiangdu People's Hospital of Yangzhou Yangzhou ChinaDepartment of Critical Care Medicine Affiliated Hospital of Nantong University Nantong ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaDepartment of Oncology Jiangdu People's Hospital of Yangzhou Yangzhou ChinaDepartment of Epidemiology School of Public Health, Nantong University Nantong Jiangsu ChinaAbstract Background and Objective To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods “Blood +” high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non‐tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL‐SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL‐SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. Results A total of 7 pQTL‐SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL‐SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL‐SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. Conclusion A total of 4 pQTL‐SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.https://doi.org/10.1002/cam4.70247lung adenocarcinomaprotein quantitative trait loci (pQTL)proteomicsSNP
spellingShingle Yutong Wu
Huiwen Xu
Liping Mao
Rongrong Zhao
Junfeng Chu
Lili Huang
Wendi Zhang
Yiran Liu
Qiong Chen
Xiaobo Tao
Siqi Li
Shenxuan Zhou
Anhui Ning
Zhenyu Li
Tian Tian
Lei Zhang
Jiahua Cui
Guangyu Tian
Minjie Chu
Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
Cancer Medicine
lung adenocarcinoma
protein quantitative trait loci (pQTL)
proteomics
SNP
title Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
title_full Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
title_fullStr Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
title_full_unstemmed Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
title_short Identification of novel pQTL‐SNPs associated with lung adenocarcinoma risk: A multi‐stage study
title_sort identification of novel pqtl snps associated with lung adenocarcinoma risk a multi stage study
topic lung adenocarcinoma
protein quantitative trait loci (pQTL)
proteomics
SNP
url https://doi.org/10.1002/cam4.70247
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