Sivagnanalingam Umayal, Demanelis Kathryn, Wang Renwei, Yuan Jian-Min, Finn Olivera J
University of Pittsburgh, Pittsburgh, United States.
University of Pittsburgh, Pittsburgh, PA, United States.
Cancer Epidemiol Biomarkers Prev. 2025 Jul 22. doi: 10.1158/1055-9965.EPI-25-0279.
There are currently no blood-based biomarkers for early detection of lung cancer. We explored cellular and soluble mediators of immune dysregulation as potential biomarkers of lung cancer risk and development. We conducted a prospective nested case-control study of incident lung cancer cases and individually matched healthy controls from the Pittsburgh Lung Screening Study (PLuSS) cohort of current and former smokers at high risk for developing lung cancer.
Peripheral blood mononuclear cells (PBMCs) were analyzed by Flow Cytometry, and Meso Scale Discovery multiplex platform immunoassay was used for detection of serum cytokines and chemokines at a distal (7 years prior) and a proximal (9 months prior) timepoint prior to cancer diagnosis. A linear mixed model was used to assess differences of analytes between cases and controls. Conditional logistic regression models were used to evaluate associations between levels of analytes and lung cancer risk.
No significant PBMC differences were found between cases and controls. Serum interleukin-6 (IL-6), IL-12/IL-23p40, IL-17A, and tumor-necrosis factor-α (TNFα) were significantly higher in cases than controls (P < 0.05) at the proximal timepoint. Cases had higher levels of angiogenic protein-placental growth factor (PlGF) in sera from both distal and proximal timepoints (P < 0.05). Doubling concentrations of these analytes were associated with a 40% to 300% increase in lung cancer risk (P < 0.05).
These circulating candidate biomarkers warrant further validation for early detection of lung cancer and identification of elevated risk.
If validated in larger studies, these biomarkers could have clinical relevance.
目前尚无用于肺癌早期检测的血液生物标志物。我们探索了免疫失调的细胞和可溶性介质，将其作为肺癌风险和发展的潜在生物标志物。我们对肺癌发病病例进行了一项前瞻性巢式病例对照研究，并从匹兹堡肺癌筛查研究（PLuSS）队列中选取了个体匹配的健康对照，该队列中的现吸烟者和曾吸烟者患肺癌风险较高。
采用流式细胞术分析外周血单个核细胞（PBMC），并使用中尺度发现多重平台免疫测定法在癌症诊断前的远端（约7年前）和近端（约9个月前）时间点检测血清细胞因子和趋化因子。使用线性混合模型评估病例和对照之间分析物的差异。使用条件逻辑回归模型评估分析物水平与肺癌风险之间的关联。
病例组和对照组之间未发现PBMC有显著差异。在近端时间点，病例组血清白细胞介素-6（IL-6）、IL-12/IL-23p40、IL-17A和肿瘤坏死因子-α（TNFα）显著高于对照组（P < 0.05）。病例组在远端和近端时间点的血清中血管生成蛋白胎盘生长因子（PlGF）水平均较高（P < 0.05）。这些分析物浓度翻倍与肺癌风险增加40%至300%相关（P < 0.05）。
这些循环候选生物标志物值得进一步验证，以用于肺癌的早期检测和高风险识别。
如果在更大规模的研究中得到验证，这些生物标志物可能具有临床意义。
