Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, 565-0871, Osaka, Japan.
Mol Cancer. 2024 Nov 7;23(1):249. doi: 10.1186/s12943-024-02159-9.
A comprehensive endoscopic small and large intestinal untargeted step biopsy procedure was conducted to compare gene expression between the normal intestinal mucosa of healthy individuals and that of patients with colorectal tumors. From 78 participants (healthy individuals [n = 17], patients with colorectal conventional adenomas [n = 6], patients with Tis-T1 colorectal cancer [n = 41], patients with T2-4 colorectal cancer [n = 14]), biopsies of normal mucosa of the terminal ileum, right-sided colon (cecum and ascending colon), and left-sided colorectum (descending colon, sigmoid colon, and rectum) were obtained using a lower gastrointestinal endoscope. RNA was extracted from all samples, and total transcriptome sequencing was performed. Transcriptome data from 388 samples was analyzed. DNA was also extracted from tumor biopsy tissues and analyzed for whole-exome sequencing. In healthy individuals, gene expression differed significantly among the terminal ileum, right-sided colon, and left-sided colorectum, presumably linked to embryological factors. There were differences in gene expression in the normal mucosa in colorectal cancer patients, compared to healthy controls. Patients with tumors, especially T2-4 colorectal cancer, showed considerable variation in gene expression in non-tumor tissues, even in the terminal ileum distant from the tumor site. Based on endoscopic biopsies, the results imply cancer-predisposing conditions in seemingly normal tissues. The present study points to the importance of small intestine and cancer-predisposing conditions in the colon of colorectal cancer patients, with possible implications for developing novel immunotherapy and other therapeutic modalities.
进行了全面的内镜小肠和大肠非靶向分步活检程序，以比较健康个体的正常肠黏膜和结直肠肿瘤患者的基因表达。从 78 名参与者（健康个体 [n=17]、结直肠传统腺瘤患者 [n=6]、Tis-T1 结直肠癌患者 [n=41]、T2-4 结直肠癌患者 [n=14]）中，使用下消化道内镜获取回肠末端、右侧结肠（盲肠和升结肠）和左侧结直肠（降结肠、乙状结肠和直肠）的正常黏膜活检。从所有样本中提取 RNA，并进行全转录组测序。分析了 388 个样本的转录组数据。还从肿瘤活检组织中提取 DNA 并进行全外显子组测序。在健康个体中，回肠、右半结肠和左半结肠之间的基因表达存在显著差异，这可能与胚胎因素有关。与健康对照组相比，结直肠癌患者的正常黏膜基因表达存在差异。与肿瘤患者，尤其是 T2-4 结直肠癌患者相比，即使在远离肿瘤部位的回肠远端，非肿瘤组织中的基因表达也存在很大差异。基于内镜活检，结果提示在看似正常的组织中存在癌症易感条件。本研究表明结直肠癌患者的小肠和结肠存在癌症易感条件的重要性，这可能对开发新的免疫疗法和其他治疗模式具有重要意义。
