Abstract：
Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.
摘要：
小细胞肺癌（SCLC）是一种高度恶性和异质性的癌症，其治疗选择和预后预测模型有限。这里,我们分析了福尔马林固定，通过蛋白质组学分析进行手术切除的石蜡包埋（FFPE）样品，并将SCLC分层为三种蛋白质组亚型(S-I，S-II,和S-III）具有不同的临床结果和化疗反应。蛋白质组分型是一个独立的预后因素，比目前的肿瘤淋巴结转移或退伍军人管理局肺研究组分期方法表现更好。亚型分型结果可以使用来自独立队列的FFPE活检样本进一步验证。将分析扩展到手术和活检样本。S-II亚型的特征特别表明免疫疗法的潜在益处。S-III中的差异过表达蛋白，预后最差的亚型，允许我们提名潜在的治疗靶点，这表明患者选择可能为以前失败的临床试验带来新的希望。最后,对接受免疫治疗的SCLC患者的独立队列的分析验证了S-II患者在一线免疫治疗后的无进展生存期和总生存期的预测.总的来说，我们的研究为未来的临床研究提供了理论基础,以验证当前的研究结果,从而更准确地预测预后和进行精确的治疗.
