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.

中文翻译：

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内窥镜肠道阶梯活检揭示的结直肠癌患者非肿瘤区域的变异性


进行全面的内窥镜小肠和大肠非靶向阶梯活检程序，比较健康个体和结直肠肿瘤患者正常肠粘膜之间的基因表达。来自 78 名参与者 （健康个体 [n = 17]、结直肠常规腺瘤患者 [n = 6]、Tis-T1 结直肠癌患者 [n = 41]、T2-4 结直肠癌患者 [n = 14]），使用下消化道内窥镜获得末端回肠、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）正常粘膜的活检。从所有样本中提取 RNA，并进行总转录组测序。分析了来自 388 个样本的转录组数据。还从肿瘤活检组织中提取 DNA 并分析用于全外显子组测序。在健康个体中，末端回肠、右侧结肠和左侧结直肠之间的基因表达存在显着差异，这可能与胚胎学因素有关。与健康对照相比，结直肠癌患者正常粘膜中的基因表达存在差异。肿瘤患者，尤其是 T2-4 型结直肠癌患者，在非肿瘤组织中的基因表达表现出相当大的差异，即使在远离肿瘤部位的末端回肠中也是如此。根据内窥镜活检，结果表明看似正常的组织存在癌症易感因素。本研究指出了结直肠癌患者结肠中小肠和癌症易感病症的重要性，这可能对开发新的免疫疗法和其他治疗方式产生影响。