Li Leijie, Zhang Yujia, Ren Yongyong, Cheng Zhiwei, Zhang Yuening, Wang Xinbo, Zhao Hongyu, Lu Hui
SJTU-Yale Joint Center for Biostatistics and Data Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Department of Biostatistics, Yale University, New Haven, CT, United States.
Front Bioeng Biotechnol. 2022 May 13;10:849798. doi: 10.3389/fbioe.2022.849798. eCollection 2022.
Upper gastrointestinal cancer (UGIC) is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Here, we collected 39,057 cells, and they were annotated into nine cell types. By clustering cancer stem cells (CSCs), we discovered the ubiquitous existence of sub-cluster CSCs in all UGICs, which is named upper gastrointestinal cancer stem cells (UGCSCs). The identification of UGCSC function is coincident with the carcinogen of UGICs. We compared the UGCSC expression profile with 215,291 single cells from six other cancers and discovered that UGCSCs are specific tumor stem cells in UGIC. Exploration of the expression network indicated that inflammatory genes (, , , and ) and Wnt pathway genes (, , , and ) are upregulated in tumor stem cells of UGICs. These results suggest a new mechanism for carcinogenesis in UGIC: mucosa damage and repair caused by poor eating habits lead to chronic inflammation, and the persistent chronic inflammation triggers the Wnt pathway; ultimately, this process induces UGICs. These findings establish the core signal pathway that connects poor eating habits and UGIC. Our system provides deeper insights into UGIC carcinogens and a platform to promote gastrointestinal cancer diagnosis and therapy.
上消化道癌（UGIC）是一种侵袭性癌症，在全球范围内发病率不断上升且预后较差。在此，我们收集了39057个细胞，并将它们注释为九种细胞类型。通过对癌症干细胞（CSCs）进行聚类分析，我们发现在所有UGIC中均普遍存在亚群癌症干细胞，我们将其命名为上消化道癌干细胞（UGCSCs）。UGCSC功能的鉴定与UGIC的致癌物一致。我们将UGCSC表达谱与来自其他六种癌症的215291个单细胞进行了比较，发现UGCSCs是UGIC中的特异性肿瘤干细胞。对表达网络的探索表明，炎症基因（、、、和）和Wnt信号通路基因（、、、和）在UGIC的肿瘤干细胞中上调。这些结果提示了UGIC致癌的一种新机制：不良饮食习惯导致的黏膜损伤和修复引发慢性炎症，持续的慢性炎症触发Wnt信号通路；最终，这一过程诱发UGIC。这些发现确立了连接不良饮食习惯和UGIC的核心信号通路。我们的系统为UGIC致癌物提供了更深入的见解，并为促进胃肠道癌症的诊断和治疗提供了一个平台。
