ID | 118926 |
Author |
Miyazaki, Katsuki
City of Hope|Tokushima University
Wada, Yuma
City of Hope|Tokushima University
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Okuno, Keisuke
City of Hope|Tokyo Medical and Dental University
Murano, Tatsuro
National Cancer Center Hospital East
Morine, Yuji
Tokushima University
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Ikemoto, Tetsuya
Tokushima University
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Saito, Yu
Tokushima University
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Ikematsu, Hiroaki
National Cancer Center Hospital East
Kinugasa, Yusuke
Tokyo Medical and Dental University
Shimada, Mitsuo
Tokushima University
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Goel, Ajay
City of Hope
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Keywords | Exosomal miRNA
Cell-free miRNA
T1 CRC
Lymph node metastasis
Liquid biopsy
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Content Type |
Journal Article
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Description | Background: According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC.
Methods: We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. Results: A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70–0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. Conclusions: Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy. |
Journal Title |
Molecular Cancer
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ISSN | 14764598
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Publisher | BioMed Central|Springer Nature
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Volume | 22
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Start Page | 2
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Published Date | 2023-01-06
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Rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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language |
eng
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departments |
University Hospital
Medical Sciences
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