Small cell lung cancer (SCLC) is a malignancy with a poor prognosis whose treatment has not progressed for decades. The survival benefit of surgery and the selection of surgical candidates are still controversial in SCLC. This study is the first report to identify transcriptomic alterations associated with prognosis and propose a gene expression-based risk signature that can be used to predict overall survival (OS) in SCLC patients who have undergone potentially curative surgery. An integrative transcriptome analysis of three gene expression datasets (GSE30219, GSE43346, and GSE149507) revealed 1734 up-regulated and 2907 down-regulated genes. Cox-Mantel test, Cox regression, and Lasso regression analyses were used to identify genes to be included in the risk signature. EGAD00001001244 and GSE60052-cohorts were used for internal and external validation, respectively. Overall survival was significantly poorer in patients with high-risk scores compared to the low-risk group. The discriminatory performance of the risk signature was superior to other parameters. Multivariate analysis showed that the risk signature has the potential to be an independent predictor of prognosis. The prognostic genes were enriched in pathways including regulation of transcription, cell cycle, cell metabolism, and angiogenesis. Determining the roles of the identified prognostic genes in the pathogenesis of SCLC may contribute to the development of new treatment strategies. The risk signature needs to be validated in a larger cohort of patients to test its usefulness in clinical decision-making.
小细胞肺癌（SCLC）是一种预后不良的恶性肿瘤，其治疗数十年来进展甚微。手术治疗的生存获益及手术适应症的选择在小细胞肺癌中仍存在争议。本研究首次报道了与预后相关的转录组学改变，并提出了一种基于基因表达的风险特征，可用于预测接受潜在根治性手术的小细胞肺癌患者的总生存期（OS）。通过对三个基因表达数据集（GSE30219、GSE43346和GSE149507）进行整合转录组分析，共发现1734个上调基因和2907个下调基因。研究采用Cox-Mantel检验、Cox回归和Lasso回归分析筛选纳入风险特征的基因，并分别使用EGAD00001001244队列和GSE60052队列进行内部和外部验证。结果显示，高风险评分患者的总生存期显著低于低风险组，且该风险特征的区分性能优于其他参数。多变量分析表明，该风险特征有望成为独立的预后预测指标。预后相关基因富集于转录调控、细胞周期、细胞代谢及血管生成等通路。明确这些预后基因在小细胞肺癌发病机制中的作用，可能有助于开发新的治疗策略。该风险特征需在更大规模患者队列中进行验证，以评估其在临床决策中的应用价值。
肿瘤(癌症)患者之家