单细胞肿瘤干性分析揭示了细胞周期和 DNA 损伤修复在两种不同类型食管癌中的作用。
Single‑cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer.
机构信息
Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000, P.R. China.
Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
出版信息
Oncol Rep. 2019 Jun;41(6):3201-3208. doi: 10.3892/or.2019.7117. Epub 2019 Apr 15.
Intratumoral heterogeneity, particularly the potential cancer stemness of single cancer cells, has not yet been fully elucidated in human esophageal cancer. Single‑cell transcriptome sequencing of two types of esophageal adenocarcinoma (EAC) and two types of esophageal squamous cell carcinoma (ESCC) tissues was performed, and the intratumoral cancer stemness of the types of esophageal cancer were characterized at the single‑cell level in the present study. By comparing the transcriptomic profiles of single cancer cells with high and low stemness in individual patients, it was revealed that the overexpression of cell cycle‑associated genes in EAC cells was highly correlated with stemness, whereas overexpression of genes involved in the signaling pathways of DNA replication and DNA damage repair was significantly correlated with stemness in ESCC. High expression of these stemness‑associated genes was correlated with poor prognosis of patients. Additionally, poly [ADP‑ribose] polymerase(PARP)4 was identified as a novel cancer stemness‑associated gene in ESCC and its association with survival was validated in a cohort of 121 patients with ESCC. These findings have profound potential implications for the use of cell cycle inhibitors in EAC and PARP inhibitors in ESCC, which may provide novel mechanistic insights into the plasticity of esophageal cancer.
肿瘤内异质性,特别是单个癌细胞的潜在癌症干性,在人类食管癌中尚未得到充分阐明。本研究对两种类型的食管腺癌(EAC)和两种类型的食管鳞癌(ESCC)组织进行了单细胞转录组测序,并在单细胞水平上对食管癌的肿瘤内癌症干性进行了特征描述。通过比较个体患者中高和低干性的单个癌细胞的转录组谱,发现 EAC 细胞中与细胞周期相关基因的过表达与干性高度相关,而参与 DNA 复制和 DNA 损伤修复信号通路的基因的过表达与 ESCC 的干性显著相关。这些干性相关基因的高表达与患者预后不良相关。此外,聚 [ADP-核糖] 聚合酶(PARP)4 被鉴定为 ESCC 中一种新的癌症干性相关基因,在 121 名 ESCC 患者的队列中验证了其与生存的关联。这些发现对 EAC 中细胞周期抑制剂和 ESCC 中 PARP 抑制剂的使用具有深远的潜在意义,可能为食管癌的可塑性提供新的机制见解。
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