Prognostic value of circulating proteins at diagnosis among patients with lung cancer: a comprehensive analysis by smoking status.

IF 4 2区医学 Q2 ONCOLOGY Translational lung cancer research Pub Date : 2024-09-30 Epub Date: 2024-09-27 DOI:10.21037/tlcr-24-242

Xiaoshuang Feng, Hilary A Robbins, Anush Mukeriya, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Jolanta Lissowska, Miodrag Ognjanovic, Beata Swiatkowska, David Zaridze, Paul Brennan, Mattias Johansson, Mahdi Sheikh

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Abstract

Background: Improved prediction of prognosis among lung cancer patients could facilitate better clinical management. We aimed to study the prognostic significance of circulating proteins at the time of lung cancer diagnosis, among patients with and without smoking history.

Methods: We measured 91 proteins using the Olink Immune-Oncology panel in plasma samples that were collected at diagnosis from 244 never smoking and 742 ever smoking patients with stage I-IIIA non-small cell lung cancer (NSCLC). Patients were recruited from nine centres in Russian Federation, Poland, Serbia, Czechia, and Romania, between 2007-2016 and were prospectively followed through 2020. We used multivariable Survey-weighted Cox models to assess the relationship between overall survival and levels of proteins by adjusting for smoking, age at diagnosis, sex, education, alcohol intake, histology, and stage.

Results: The 5-year survival rate was higher among never than ever smoking patients (63.1% vs. 46.6%, P<0.001). In age- and sex-adjusted survival analysis, 23 proteins were nominally associated with overall survival, but after adjustment for potential confounders and correcting for multiple testing, none of the proteins showed a significant association with overall survival. In stratified analysis by smoking status, IL8 [hazard ratio (HR) per standard deviation (SD): 1.40, 95% confidence interval (CI): 1.18-1.65, P=1×10^-4] and hepatocyte growth factor (HGF) (HR: 1.45, 95% CI: 1.18-1.79, P=5×10^-4) were associated with survival among never smokers, but no protein was found associated with survival among ever smokers. Integrating proteins into the models with clinical risk factors did not improve the predictive performance of NSCLC prognosis [C-index of 0.63 (clinical) vs. 0.64 (clinical + proteins) for ever smokers, P=0.20; C-index of 0.68 (clinical) vs. 0.72 (clinical + proteins) for never smokers, P=0.28].

Conclusions: We found limited evidence of a potential for circulating immune- and cancer-related protein markers in lung cancer prognosis. Whereas some specific proteins appear to be uniquely associated with lung cancer survival in never smokers.

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肺癌患者诊断时循环蛋白的预后价值：按吸烟状况进行的综合分析。

背景：改善肺癌患者的预后预测有助于更好地进行临床治疗。我们的目的是研究有吸烟史和无吸烟史的肺癌患者在确诊时循环蛋白对预后的意义：方法：我们使用 Olink 免疫肿瘤面板检测了 244 名从不吸烟和 742 名曾经吸烟的 I-IIIA 期非小细胞肺癌（NSCLC）患者诊断时采集的血浆样本中的 91 种蛋白质。2007 年至 2016 年期间，我们从俄罗斯联邦、波兰、塞尔维亚、捷克和罗马尼亚的九个中心招募了患者，并对他们进行了前瞻性随访，直至 2020 年。我们使用多变量调查加权 Cox 模型评估了总生存率与蛋白质水平之间的关系，并对吸烟、诊断时的年龄、性别、教育程度、酒精摄入量、组织学和分期进行了调整：从未吸烟者的5年生存率高于曾经吸烟者（63.1%对46.6%，P-4），肝细胞生长因子（HGF）（HR：1.45，95% CI：1.18-1.79，P=5×10-4）与从未吸烟者的生存率相关，但未发现任何蛋白质与曾经吸烟者的生存率相关。将蛋白质与临床风险因素整合到模型中并没有提高NSCLC预后的预测性能[对于从不吸烟者，C指数为0.63（临床）对0.64（临床+蛋白质），P=0.20；对于从不吸烟者，C指数为0.68（临床）对0.72（临床+蛋白质），P=0.28]：我们发现，循环免疫和癌症相关蛋白标记物在肺癌预后中的潜在作用证据有限。而一些特定的蛋白质似乎与从不吸烟者的肺癌生存率有独特的关联。

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来源期刊

Translational lung cancer research Medicine-Oncology

CiteScore

7.20

自引率

2.50%

发文量

137

期刊介绍： Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.