State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Cancer Cell. 2023 Jan 9;41(1):181-195.e9. doi: 10.1016/j.ccell.2022.12.004. Epub 2022 Dec 29.
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 distribution 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.
对人类癌症的综合分子分析为癌症患者的精确管理提供了分子分类。在这里，我们分析了 155 例食管鳞癌（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 分为四个亚型：细胞周期途径激活、NRF2 致癌激活、免疫抑制（IS）和免疫调节（IM）。IS 和 IM 病例高度免疫浸润，但免疫细胞的类型和分布不同。在临床试验中，与其他亚型相比，IM 病例对免疫检查点阻断治疗的反应更好。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，该分类器对抗 PD-1 治疗的反应具有 85.7%的敏感性和 90%的特异性。这些结果强调了基于多组学数据进行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。
