Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma
Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma
复制标题
综合多组学分析为食管鳞状细胞癌提供临床相关的分子分类
DOI：
10.1016/j.ccell.2022.12.004
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发表时间：
2023-01-09
期刊：
影响因子：
50.3
通讯作者：
Zhan, Qimin
中科院分区：
文献类型：
--
作者：
Liu, Zhihuai;Zhao, Yahui;Zhan, Qimin
人类癌症的综合分子分析已经产生了用于癌症患者精确管理的分子分类。在这里，我们分析了155例食管鳞状细胞癌（ESCC）的全基因组、表观基因组、转录组和蛋白质组数据。多组学分析将ESCC分为四种亚型：细胞周期途径激活、NRF 2致癌激活、免疫抑制（IS）和免疫调节（IM）。IS和IM均为高度免疫浸润，但免疫细胞的类型和分布不同。在临床试验中，IM病例对免疫检查点阻断治疗的反应优于其他亚型。我们进一步开发了一个具有28个特征的分类器来识别IM亚型，该分类器预测抗PD-1治疗反应的灵敏度为85.7%，特异性为90%。这些结果强调了基于多组学数据的无偏分子分类的临床价值，并有可能进一步提高对ESCC的理解和治疗。
Integrated molecular analysis of human cancer has yielded molecular classification for precise management of cancer patients. Here, we analyzed the whole genomic, epigenomic, transcriptomic, and proteomic data of 155 esophageal squamous cell carcinomas (ESCCs). Multi-omics analysis led to the classification of ESCCs into four subtypes: cell cycle pathway activation, NRF2 oncogenic activation, immune suppression (IS), and immune modulation (IM). IS and IM cases were highly immune infiltrated but differed in the type and distribu-tion of immune cells. IM cases showed better response to immune checkpoint blockade therapy than other subtypes in a clinical trial. We further developed a classifier with 28 features to identify the IM subtype, which predicted anti-PD-1 therapy response with 85.7% sensitivity and 90% specificity. These results emphasize the clinical value of unbiased molecular classification based on multi-omics data and have the potential to further improve the understanding and treatment of ESCC.