Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer.
Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer.
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DOI：
10.1158/0008-5472.can-20-3454
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发表时间：
2021-07-01
期刊：
影响因子：
11.2
通讯作者：
Chadeau-Hyam M
中科院分区：
文献类型：
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作者：
Dagnino S;Bodinier B;Guida F;Smith-Byrne K;Petrovic D;Whitaker MD;Haugdahl Nøst T;Agnoli C;Palli D;Sacerdote C;Panico S;Tumino R;Schulze MB;Johansson M;Keski-Rahkonen P;Scalbert A;Vineis P;Johansson M;Sandanger TM;Vermeulen RCH;Chadeau-Hyam M
越来越多的证据表明炎症在肺癌发生中的作用。少数循环炎性蛋白已被确定为在肺癌诊断前显示出升高的水平，表明前瞻性循环蛋白浓度作为早期致癌的标志物的潜力。为了确定肺癌风险的新标志物，我们测量了意大利和挪威（仅女性）两个前瞻性队列的648份诊断前血液样本中的92种循环炎症蛋白。为了保持结果的可比性并防止混淆因素，在两项研究的女性中进行了主要统计分析，并在男性（意大利参与者）中进行了复制。单变量和惩罚回归模型首次揭示了与对照组相比，继续发展为肺癌的病例中CDCP 1蛋白的血液水平更高，无论诊断时间，吸烟习惯和性别如何。在另外450个样本中验证了这种关联。对于未来的腺癌病例，CDCP 1显示出更好的解释性能，相关性更强。综合分析结合基因表达和蛋白水平CDCP 1在同一个人中测量表明CDCP 1和LRRN 3和SEM 1的转录本的表达之间的联系。富集分析表明CDCP 1在与细胞粘附和移动性相关的途径中具有潜在作用，例如WNT/β-连环蛋白途径。总的来说，这项研究在诊断前几年就确定了肺癌相关的CDCP 1表达失调。
Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. In order to identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 pre-diagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared to controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer-related dysregulation of CDCP1 expression years before diagnosis.