Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research. This report describes a novel 19-gene signature (19-GCS) that predicts stage I lung adenocarcinoma (LAC) recurrence and response to therapy and performs comparably in pancreatic adenocarcinoma (PAC), which shares LAC molecular traits. Kaplan–Meier, Cox regression, and cross-validation analyses were used to build the signature from training, test, and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets. A statistical analysis was performed using the R language. Pathway and gene set enrichment were used to identify underlying mechanisms. 19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC (P=0.002 and P<0.001, respectively) and in stage I–II PAC (P<0.0001 and P<0.0005, respectively). A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors. Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation, enhanced stemness, DNA repair deficiency, and compromised MHC class I and II antigen presentation along with decreased immune infiltration. Importantly, high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additional benefit from FOLFIRINOX compared with gemcitabine-based regimens. When validated prospectively, this proof-of-concept biomarker may contribute to tailoring treatment, recurrence reduction, and survival improvements in early-stage lung and pancreatic cancers.

中文翻译：

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反向工程化预测特征，其特征在于增殖，DNA损伤和I期肺腺癌复发的免疫逃逸。

识别有进展风险的早期癌症患者是生物标志物研究的主要目标。该报告描述了一种新颖的19基因标记（19-GCS），该标记可预测I期肺腺癌（LAC）的复发和对治疗的反应，并且在具有LAC分子特征的胰腺腺癌（PAC）中具有可比性。使用Kaplan–Meier，Cox回归和交叉验证分析从训练，测试和验证集构建签名，这些集包括来自多个独立数据集的831个I期LAC转录组。使用R语言进行了统计分析。途径和基因集富集用于鉴定潜在机制。19-GCS强烈预测I LAC期的总体生存率和无复发生存率（P = 0.002和P分别<0.001）和I–II阶段PAC（P <0.0001和P分别<0.0005）。多元Cox回归分析表明19-GCS与重要的临床因素无关。通路分析表明，19-GCS高危LAC和PAC肿瘤的特征在于增殖增加，干性增强，DNA修复缺陷，MHC I类和II类MHC抗原呈递受损以及免疫浸润减少。重要的是，与基于吉西他滨的方案相比，高风险的LAC患者似乎没有从顺铂辅助治疗中获益，而PAC患者从FOLFIRINOX获得了额外的益处。如果经过前瞻性验证，则该概念证明生物标志物可能有助于早期肺癌和胰腺癌的定制治疗，减少复发和改善生存率。