Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing  

作　　者：Quan Wang Zhu Wang Zhen Zhang Wei Zhang Mengmeng Zhang Zhanlong Shen Yingjiang Ye Kewei Jiang Shan Wang 

机构地区：[1]Department of Gastroenterological Surgery,Peking University People’s Hospital,Beijing 100044,China [2]Laboratory of Surgical Oncology,Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research,Peking University People’s Hospital,Beijing 100044,China [3]Department of Gastrointestinal Surgery,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China

出　　处：《Chinese Journal of Cancer Research》2021年第2期271-288,共18页中国癌症研究（英文版）

基　　金：supported by National Key Research and Development Program of China(No.2017YFC1308800);Industry-University-Research Innovation Fund in Ministry of Education of the People’s Republic of China(No.2018A01013)。

摘　　要：Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.

关 键 词：Ulcerative colitis-associated colon cancer single-cell RNA sequencing cell heterogeneity evolutionary trajectory 

分 类 号：R735.35[医药卫生—肿瘤]