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

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-09-18 DOI:10.1002/cam4.70247

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

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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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背景和目的探讨蛋白质定量性状位点（pQTL-SNPs）与 LUAD 风险之间的关联。方法对女性 LUAD 患者和女性健康对照者的血浆进行 "血液+"高深度血液蛋白质组学分析，并结合女性 LUAD 患者肿瘤和邻近非肿瘤组织的蛋白质组学数据，筛选在血浆和组织中均匀表达的蛋白质。选定的 pQTL-SNPs 与 LUAD 风险之间的关联由亚洲女性肺癌联盟 GWAS（FLCCA GWAS）进行评估。酶联免疫吸附试验（ELISA）用于测定候选蛋白的水平。结果共有 7 个 pQTL-SNPs 与 LUAD 风险的改变显著相关（p < 0.05）。同时，在 LUAD 病例的血浆和肿瘤组织中，其相应靶蛋白的表达均有所下降，这可能是肿瘤抑制蛋白在起作用。3个pQTL-SNPs（rs7683000、rs73224660和rs2776937）突变后，相应的靶蛋白BST1和NRP1的表达均下降，作为潜在的肿瘤抑制蛋白，可能会促进肿瘤的发生，进一步增加患LUAD的风险（OR >1，p < 0.05）；而另一个pQTL-SNP rs62069916突变后，相应的靶蛋白APOH表达增加，同时作为潜在的肿瘤抑制蛋白，可能抑制肿瘤发生，进一步降低了LUAD的发病风险（OR <1，p <0.05）。此外，NRP1 和 APOH 在 LUAD 细胞系中的表达显著下降，在 LUAD 患者血浆中的表达也得到了验证。结论共有 4 个 pQTL-SNPs（rs7683000、rs73224660、rs2776937 和 rs62069916）可能通过调节突变后目标蛋白（BST1、NRP1 和 APOH）的表达与 LUAD 风险的改变有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.