基于普通转录组和单细胞转录组测序解析间质型胃癌复发风险相关的肿瘤细胞及微环境特征  

Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq

作　　者：潘雨薇 谭玉婷 薛锐 储召乐 刘碧颖 李先锋 王涛[3] 王斌 张璇[4] 杨永涛 PAN Yuwei;TAN Yuting;XUE Rui;CHU Zhaole;LIU Biying;LI Xianfeng;WANG Tao;WANG Bin;ZHANG Xuan;YANG Yongtao(School of Medicine,Chongqing University,Chongqing;Department of Gastroenterology,Chongqing University Cancer Hospital,Chongqing;Department of Gastroenterology,Chongqing Key Laboratory of Precise Prevention and Treatment of Digestive Malignancies,Army Medical Center of PLA/Daping Hospital of Third Military Medical University,Chongqing;Department of Oncology,Chongqing Hospital of Traditional Chinese Medicine,Chongqing,China)

机构地区：[1]重庆大学医学院,重庆 [2]重庆大学附属肿瘤医院消化内科,重庆 [3]陆军特色医学中心(第三军医大学大坪医院)消化内科,消化系统肿瘤精准防治重庆市重点实验室,重庆 [4]重庆市中医院肿瘤科,重庆

出　　处：《陆军军医大学学报》2025年第5期443-452,共10页Journal of Army Medical University

基　　金：国家自然科学基金优秀青年科学项目(81822032);重庆市杰出青年基金项目(CSTC2019JCYJJQX0027)。

摘　　要：目的整合多组学数据解析间质型胃癌(mesenchymal-subtype gastric cancer,Mes-GC)临床特性,探究与间质型胃癌复发风险相关的肿瘤细胞及微环境特征。方法收集2022年1月至2023年12月,在陆军特色医学中心消化内科就诊患者的组织样本,包括19例弥漫型胃癌、22例肠型胃癌与23例混合型胃癌患者的组织,用于转录组和基因组测序;整合包括癌症基因组图谱(The Cancer Genome Atlas,TCGA)、美国国立生物技术信息中心基因表达数据库(Gene Expression Omnibu,GEO)以及国家基因组科学中心(National Genomics Data Center,NGDC)数据库资源,采用生物信息学分析,比较间质型胃癌与非间质型胃癌在临床特性以及肿瘤微环境特征等方面的异同。结果相比非间质型胃癌,间质型胃癌临床分期较晚、肿瘤浸润程度深、淋巴结转移率高(P<0.05);Kaplan-Meier生存分析表明间质型胃癌生存期短、极易复发、临床预后差(P<0.05);单细胞转录组测序(single-cell RNA sequencing,scRNA-seq)数据分析揭示了间质型胃癌肿瘤细胞高表达干性、转移以及上皮-间质转化(epithelial-mesenchymal transition,EMT)相关基因,肿瘤微环境中髓系细胞、平滑肌细胞、内皮细胞和成纤维细胞显著升高,其中成纤维细胞含量升高最为明显(P<0.05),且成纤维细胞含量越高患者预后越差。结论间质型胃癌肿瘤细胞具有较高的干性和EMT特征,肿瘤微环境中富集髓系细胞、内皮细胞和成纤维细胞等间质细胞,这些特征可能是导致间质型胃癌预后差、易复发的关键因素。Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor pr

关 键 词：间质型胃癌 肿瘤微环境 生物信息学 预后 

分 类 号：R394.3[医药卫生—医学遗传学] R730.7[医药卫生—基础医学] R735.2