Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Cancer Institute of the Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao, P. R. China.
Nat Commun. 2021 Jun 18;12(1):3785. doi: 10.1038/s41467-021-24043-6.
Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms of RB1 disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated by ASCL1 and NEUROD1 define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.
原发性食管小细胞癌（PSCCE）是一种致命的神经内分泌癌。先前的研究提出 PSCCE 与食管鳞状细胞癌（ESCC）之间存在遗传相似性，但对临床病程和神经内分泌分化的差异提供的证据很少。我们对 46 例 PSCCE 病例进行了全外显子组测序、RNA 测序和免疫组织化学分析。综合分析发现，98%（45/46）的病例存在 RB1 破坏的多种机制。PSCCE 的转录组图谱与小细胞肺癌（SCLC）非常相似，但与 ESCC 或食管腺癌（EAC）不同。由 ASCL1 和 NEUROD1 调控的不同基因表达模式定义了两个分子亚型，PSCCE-A 和 PSCCE-N，它们与 SCLC 亚型高度相似。在 PSCCE 中广泛观察到 T 细胞排斥表型。总之，PSCCE 具有与 SCLC 高度相似的基因组改变、转录组特征和分子亚型，但与 ESCC 或 EAC 不同。这些观察结果与肿瘤发生机制和治疗脆弱性有关。
