小细胞肺癌预后和治疗方案的蛋白质组学分层

Zitian Huo, Yaqi Duan, Dongdong Zhan, Xizhen Xu, Nairen Zheng, Jing Cai, Ruifang Sun, Jianping Wang, Fang Cheng, Zhan Gao, Caixia Xu, Wanlin Liu, Yuting Dong, Sailong Ma, Qian Zhang, Yiyun Zheng, Liping Lou, Dong Kuang, Qian Chu, Jun Qin, Guoping Wang, Yi Wang
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摘要

小细胞肺癌(SCLC)是一种高度恶性的异质性癌症,治疗方案和预后预测模型都很有限。在这里,我们通过蛋白质组学分析对福尔马林固定、石蜡包埋(FFPE)的手术切除样本进行了分析,并将小细胞肺癌分为三种蛋白质组学亚型(S-I、S-II 和 S-III),其临床预后和化疗反应各不相同。蛋白质组亚型是一个独立的预后因素,其效果优于目前的肿瘤-结节-转移或退伍军人管理局肺研究小组分期方法。亚型分析结果可通过使用来自一个独立队列的FFPE活检样本进一步验证,从而将分析范围扩大到手术样本和活检样本。特别是S-II亚型的特征表明,免疫疗法有可能带来益处。S-III亚型是预后最差的亚型,其不同程度的蛋白过表达使我们能够确定潜在的治疗靶点,这表明患者的选择可能会为之前失败的临床试验带来新的希望。最后,对接受过免疫治疗的独立 SCLC 患者队列的分析验证了 S-II 患者在接受一线免疫治疗后无进展生存期和总生存期更长的预测。总之,我们的研究为未来的临床研究提供了理论依据,以验证目前的研究结果,从而获得更准确的预后预测和精确治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer.

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.

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