血浆蛋白是复杂疾病的潜在生物标志物。我们旨在鉴定肺癌的血浆蛋白标志物。我们调查了29,266例欧洲人肺癌病例和56,450名对照组之间1130种蛋白质的基因预测血浆水平与肺癌风险的关联。对于与肺癌风险显著相关的蛋白质，我们评估了其编码基因的基因预测表达与肺癌风险的关联。在虚假发现率（FDR）<0.05的条件下，我们确定了9种血浆蛋白通过基因预测血浆水平与总体肺癌风险显著关联。蛋白质C2、MICA、AIF1和CTSH与肺癌风险增加相关，而蛋白质SFTPB、HLA-DQA2、MICB、NRP1和GMFG与肺癌风险降低相关。组织学类型的分层分析显示了这九个关联的亚型一致性，并发现一种额外的蛋白质ICAM5与肺腺癌风险显著关联（FDR <0.05）。NRP1和ICAM5蛋白质的编码基因位于以前GWAS没有报道过的两个位点。基因C2、AIF1和CTSH的基因预测血液水平与肺癌风险相关，并在蛋白质水平分析中显示结果一致。新型血浆蛋白标志物的鉴定为肺癌的生物学研究提供了新的见解。 ©2023. 作者授予Springer Nature Limited 独家许可。

Plasma proteins are potential biomarkers for complex diseases. We aimed to identify plasma protein biomarkers for lung cancer.We investigated genetically predicted plasma levels of 1130 proteins in association with lung cancer risk among 29,266 cases and 56,450 controls of European descent. For proteins significantly associated with lung cancer risk, we evaluated associations of genetically predicted expression of their coding genes with the risk of lung cancer.Nine proteins were identified with genetically predicted plasma levels significantly associated with overall lung cancer risk at a false discovery rate (FDR) of <0.05. Proteins C2, MICA, AIF1, and CTSH were associated with increased lung cancer risk, while proteins SFTPB, HLA-DQA2, MICB, NRP1, and GMFG were associated with decreased lung cancer risk. Stratified analyses by histological types revealed the cross-subtype consistency of these nine associations and identified an additional protein, ICAM5, significantly associated with lung adenocarcinoma risk (FDR < 0.05). Coding genes of NRP1 and ICAM5 proteins are located at two loci that have never been reported by previous GWAS. Genetically predicted blood levels of genes C2, AIF1, and CTSH were associated with lung cancer risk, in directions consistent with those shown in protein-level analyses.Identification of novel plasma protein biomarkers provided new insights into the biology of lung cancer.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.