Nat Commun. 2023 Jun 1;14(1):3042. doi: 10.1038/s41467-023-37979-8.
Identification of risk biomarkers may enhance early detection of smoking-related lung cancer. We measured between 392 and 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia. We identify 36 proteins with independently reproducible associations with risk of imminent lung cancer diagnosis (all p < 4 × 10). These include a few markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) that have previously been reported in studies using pre-diagnostic blood samples for lung cancer. The 36 proteins include several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation range from 1.31 for IGFBP-1 (95% CI: 1.17-1.47) to 2.43 for CEACAM5 (95% CI: 2.04-2.89). We map the 36 proteins to the hallmarks of cancer and find that activation of invasion and metastasis, proliferative signaling, tumor-promoting inflammation, and angiogenesis are most frequently implicated.
识别风险生物标志物可能有助于提高对与吸烟有关的肺癌的早期检测。我们在 731 个病例对照研究中，测量了最多 3 年前采集的血液样本中的 392 到 1162 种蛋白质，这些病例对照研究嵌套在来自美国、欧洲、新加坡和澳大利亚的六个前瞻性队列中。我们确定了 36 种与即将发生的肺癌诊断风险具有独立重现性关联的蛋白质（所有 p 值均小于 4×10）。这些标志物包括一些之前在使用肺癌诊断前血液样本的研究中报道过的标志物（如 CA-125/MUC-16 和 CEACAM5/CEA）。这 36 种蛋白包括几种生长因子（如 HGF、IGFBP-1、IGFBP-2）、肿瘤坏死因子受体（如 TNFRSF6B、TNFRSF13B）和趋化因子和细胞因子（如 CXL17、GDF-15、SCF）。每个标准差的比值范围从 IGFBP-1 的 1.31（95%CI：1.17-1.47）到 CEACAM5 的 2.43（95%CI：2.04-2.89）。我们将这 36 种蛋白映射到癌症的标志性特征上，发现侵袭和转移的激活、增殖信号、促进肿瘤的炎症和血管生成最常涉及。
