Sasaki Atsuhiro, Kuroha Masatake, Tosa Masaki, Takahashi Seiichi, Oomori Shinya, Nomura Eiki, Kikuchi Tatsuya, Onodera Motoyuki, Sato Yuichiro, Miyazawa Teruko, Chiba Hirofumi, Yokoyama Naonobu, Kusaka Jun, Okamoto Daisuke, Handa Tomoyuki, Sugimura Mikako, Iwabuchi Masahiro, Hiramoto Keiichiro, Shirota Hidekazu, Iwaki Hideya, Nagai Hiroshi, Shimoyama Yusuke, Naito Takeo, Moroi Rintaro, Shiga Hisashi, Kakuta Yoichi, Kinouchi Yoshitaka, Masamune Atsushi
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Gastroenterology, Iwaki City Medical Center, Iwaki, Japan.
Clin Transl Sci. 2025 Jun;18(6):e70270. doi: 10.1111/cts.70270.
Exosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long-term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single-center cohort study, two exosomal miRNAs (miR-4284 and miR-5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR-4284, miR-5100, miR-1246, and miR-1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65-0.83) versus 0.79 (95% confidence interval: 0.70-0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74-0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.
外泌体微小RNA（miRNA）是液体活检的候选对象。类器官培养系统能够使结肠上皮长期扩增。本研究评估了来自结直肠癌类器官的外泌体miRNA用于液体活检的情况。从正常结肠和结直肠癌组织中建立类器官。从条件培养基中分离出外泌体。从外泌体中提取miRNA并使用微阵列分析进行比较。在单个机构比较了健康患者和结直肠癌患者血清中外泌体miRNA的表达水平。使用在结直肠癌患者血清中上调的miRNA以及据报道在结直肠腺瘤类器官和血清中上调的外泌体miRNA对多中心研究进行了验证。共有44种外泌体miRNA在正常结直肠上皮细胞和结直肠癌类器官中均有共同表达，而59种仅在结直肠癌类器官中表达。在一项单中心队列研究中，两种外泌体miRNA（miR-4284和miR-5100）在结直肠癌患者血清中上调。在一项多中心研究中，四种外泌体miRNA（miR-4284、miR-5100、miR-1246和miR-1290）在结直肠癌患者血清中上调。这四种外泌体miRNA的组合与癌胚抗原具有相当的诊断性能，曲线下面积为0.75（95%置信区间：0.65 - 0.83），而癌胚抗原的曲线下面积为0.79（95%置信区间：0.70 - 0.87）。将这四种miRNA与癌胚抗原联合使用可提高诊断准确性，曲线下面积为0.82（95%置信区间：0.74 - 0.89）。源自结直肠癌类器官的外泌体miRNA可作为结直肠癌的诊断生物标志物。
