机构:[1]Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000[2]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032昆明医科大学附属第一医院[3]Department of Clinical Laboratory, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000[4]Department of Child Health Care, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
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.
基金:
The present work was supported by grants from the
Hangzhou Health Science and Technology Project (grant
no. 2017A28), Zhejiang Health Science and Technology
Project (grant no. 20180533B64), National Natural Science
Foundation of China (grant nos. 81672994 and 31860306),
Zhejiang Provincial Foundation for Natural Sciences (grant
nos. LY14H160005 and LZ15H220001) and the Zhejiang
Provincial Medical Scientific Research Foundation of China
(grant nos. 2015KYB325 and 2015PYA009).
第一作者机构:[1]Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000[2]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032
通讯作者:
通讯机构:[1]Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000[2]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032[3]Department of Clinical Laboratory, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 320000[4]Department of Child Health Care, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China[*1]Cancer Research Institute, Hangzhou Cancer Hospital, 34 Yan-Guan Street, Shang-Cheng, Hangzhou, Zhejiang 320000, P.R. China[*2]Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan 650032, P.R. China
推荐引用方式(GB/T 7714):
HONGJIN WU,YING LI,QIANG HOU,et al.Single-cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer[J].ONCOLOGY REPORTS.2019,41(6):3201-3208.doi:10.3892/or.2019.7117.
APA:
HONGJIN WU,YING LI,QIANG HOU,RONGJIN ZHOU,ZIWEI LI...&MINGFENG JIANG.(2019).Single-cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer.ONCOLOGY REPORTS,41,(6)
MLA:
HONGJIN WU,et al."Single-cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer".ONCOLOGY REPORTS 41..6(2019):3201-3208