Variability in non-tumor areas of colorectal cancer patients as revealed by endoscopic intestinal step biopsies

IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cancer Pub Date : 2024-11-07 DOI:10.1186/s12943-024-02159-9
Shoko Ikuta, Yutaka Saito, So Takata, Yoichiro Nakatani, Izumi Nagatomo, Satoshi Shiba, Yoshito Takeda, Yasushi Totoki, Sayaka Mizutani, Hironori Sunakawa, Hiroaki Ikematsu, Hiroyuki Takamaru, Atsushi Kumanogoh, Shinichi Yachida
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Abstract

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.
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内窥镜肠道阶梯活检显示的结直肠癌患者非肿瘤区域的变异性
为了比较健康人的正常肠粘膜与结直肠肿瘤患者的肠粘膜之间的基因表达,我们进行了一次全面的内窥镜小肠和大肠非靶向阶梯活检。使用下消化道内窥镜从 78 名参与者(健康人 [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])中获取了回肠末端、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)正常粘膜的活组织切片。从所有样本中提取 RNA,并进行总转录组测序。分析了 388 个样本的转录组数据。还从肿瘤活检组织中提取了 DNA,并进行了全基因组测序分析。在健康人中,回肠末端、右侧结肠和左侧结直肠的基因表达存在显著差异,这可能与胚胎学因素有关。与健康对照组相比,结直肠癌患者正常粘膜的基因表达存在差异。肿瘤患者,尤其是 T2-4 结直肠癌患者,其非肿瘤组织中的基因表达有相当大的差异,甚至在远离肿瘤部位的回肠末端也是如此。根据内窥镜活检结果,这些结果表明在看似正常的组织中也存在易患癌症的条件。本研究指出了小肠和大肠癌患者结肠中癌症易感条件的重要性,这对开发新型免疫疗法和其他治疗方法可能具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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