Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study
ABSTRACT 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 c...
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Wiley
2025-06-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70270 |
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| author | Atsuhiro Sasaki Masatake Kuroha Masaki Tosa Seiichi Takahashi Shinya Oomori Eiki Nomura Tatsuya Kikuchi Motoyuki Onodera Yuichiro Sato Teruko Miyazawa Hirofumi Chiba Naonobu Yokoyama Jun Kusaka Daisuke Okamoto Tomoyuki Handa Mikako Sugimura Masahiro Iwabuchi Keiichiro Hiramoto Hidekazu Shirota Hideya Iwaki Hiroshi Nagai Yusuke Shimoyama Takeo Naito Rintaro Moroi Hisashi Shiga Yoichi Kakuta Yoshitaka Kinouchi Atsushi Masamune |
| author_facet | Atsuhiro Sasaki Masatake Kuroha Masaki Tosa Seiichi Takahashi Shinya Oomori Eiki Nomura Tatsuya Kikuchi Motoyuki Onodera Yuichiro Sato Teruko Miyazawa Hirofumi Chiba Naonobu Yokoyama Jun Kusaka Daisuke Okamoto Tomoyuki Handa Mikako Sugimura Masahiro Iwabuchi Keiichiro Hiramoto Hidekazu Shirota Hideya Iwaki Hiroshi Nagai Yusuke Shimoyama Takeo Naito Rintaro Moroi Hisashi Shiga Yoichi Kakuta Yoshitaka Kinouchi Atsushi Masamune |
| author_sort | Atsuhiro Sasaki |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-b99b9b1ca8c94daa86e194bf2ac15772 |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-b99b9b1ca8c94daa86e194bf2ac157722025-08-20T03:28:00ZengWileyClinical and Translational Science1752-80541752-80622025-06-01186n/an/a10.1111/cts.70270Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional StudyAtsuhiro Sasaki0Masatake Kuroha1Masaki Tosa2Seiichi Takahashi3Shinya Oomori4Eiki Nomura5Tatsuya Kikuchi6Motoyuki Onodera7Yuichiro Sato8Teruko Miyazawa9Hirofumi Chiba10Naonobu Yokoyama11Jun Kusaka12Daisuke Okamoto13Tomoyuki Handa14Mikako Sugimura15Masahiro Iwabuchi16Keiichiro Hiramoto17Hidekazu Shirota18Hideya Iwaki19Hiroshi Nagai20Yusuke Shimoyama21Takeo Naito22Rintaro Moroi23Hisashi Shiga24Yoichi Kakuta25Yoshitaka Kinouchi26Atsushi Masamune27Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDepartment of Gastroenterology Iwaki City Medical Center Iwaki JapanDepartment of Gastroenterology Iwaki City Medical Center Iwaki JapanDepartment of Gastroenterology Japanese Red Cross Sendai Hospital Sendai JapanDepartment of Gastroenterology Sendai City Hospital Sendai JapanDepartment of Gastroenterology Sendai City Hospital Sendai JapanDepartment of Gastroenterology Osaki Citizen Hospital Osaki JapanDepartment of Gastroenterology Osaki Citizen Hospital Osaki JapanDepartment of Gastroenterology Japan Community Healthcare Organization, Sendai South Hospital Sendai JapanDepartment of Gastroenterology Iwate Prefectural Isawa Hospital Oshu JapanDepartment of Gastroenterology Iwate Prefectural Iwai Hospital Ichinoseki JapanDepartment of Gastroenterology Miyagi Cancer Center Natori JapanDepartment of Gastroenterology Shirakawa Kosei General Hospital Shirakawa JapanDepartment of Internal Medicine Kurihara Central Hospital Kurihara JapanDepartment of Gastroenterology NHO Sendai Medical Center Sendai JapanDepartment of Gastroenterology NHO Sendai Medical Center Sendai JapanDepartment of Gastroenterology South Miyagi Medical Center Ohgawara JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanStudent Healthcare Center, Institute for Excellence in Higher Education Tohoku University Sendai JapanDivision of Gastroenterology Tohoku University Graduate School of Medicine Sendai JapanABSTRACT 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.https://doi.org/10.1111/cts.70270carcinoembryonic antigenmiR‐1246miR‐1290miR‐4284miR‐5100 |
| spellingShingle | Atsuhiro Sasaki Masatake Kuroha Masaki Tosa Seiichi Takahashi Shinya Oomori Eiki Nomura Tatsuya Kikuchi Motoyuki Onodera Yuichiro Sato Teruko Miyazawa Hirofumi Chiba Naonobu Yokoyama Jun Kusaka Daisuke Okamoto Tomoyuki Handa Mikako Sugimura Masahiro Iwabuchi Keiichiro Hiramoto Hidekazu Shirota Hideya Iwaki Hiroshi Nagai Yusuke Shimoyama Takeo Naito Rintaro Moroi Hisashi Shiga Yoichi Kakuta Yoshitaka Kinouchi Atsushi Masamune Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study Clinical and Translational Science carcinoembryonic antigen miR‐1246 miR‐1290 miR‐4284 miR‐5100 |
| title | Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study |
| title_full | Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study |
| title_fullStr | Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study |
| title_full_unstemmed | Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study |
| title_short | Evaluation of Organoid‐Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross‐Sectional Study |
| title_sort | evaluation of organoid derived exosomal microrna as liquid biopsy for colorectal cancer a multicenter cross sectional study |
| topic | carcinoembryonic antigen miR‐1246 miR‐1290 miR‐4284 miR‐5100 |
| url | https://doi.org/10.1111/cts.70270 |
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