Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection

Abstract After endoscopic resection of T1 colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM), additional surgery is required. However, the actual frequency of LNM based on conventional risk factors is less than 16%. There is a need for biomarkers to identify T1 CRC carrying a hi...

Full description

Saved in:
Bibliographic Details
Main Authors: Kazuaki Okamoto, Hiroaki Nozawa, Tsuyoshi Ozawa, Yoko Yamamoto, Yuichiro Yokoyama, Shigenobu Emoto, Koji Murono, Kazuhito Sasaki, Mitsuhiro Fujishiro, Soichiro Ishihara
Format: Article
Language:English
Published: Nature Publishing Group 2025-02-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02348-5
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850190933201518592
author Kazuaki Okamoto
Hiroaki Nozawa
Tsuyoshi Ozawa
Yoko Yamamoto
Yuichiro Yokoyama
Shigenobu Emoto
Koji Murono
Kazuhito Sasaki
Mitsuhiro Fujishiro
Soichiro Ishihara
author_facet Kazuaki Okamoto
Hiroaki Nozawa
Tsuyoshi Ozawa
Yoko Yamamoto
Yuichiro Yokoyama
Shigenobu Emoto
Koji Murono
Kazuhito Sasaki
Mitsuhiro Fujishiro
Soichiro Ishihara
author_sort Kazuaki Okamoto
collection DOAJ
description Abstract After endoscopic resection of T1 colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM), additional surgery is required. However, the actual frequency of LNM based on conventional risk factors is less than 16%. There is a need for biomarkers to identify T1 CRC carrying a high risk of metastasis to avoid unnecessary radical surgery. Based on the comparison of serum miRNA between stage I/II and stage III from a large-scale in silico dataset, we conducted a validation analysis of the selected miRNAs using plasma samples from LNM-positive and LNM-negative T1 CRC patients who underwent endoscopic treatment followed by radical surgery at our hospital. In the validation cohort, the three-miRNA classifiers (miR-195-5p, miR-221-3p, and miR-193b-3p) effectively identified LNM-positive T1 CRC patients who received upfront surgery with an area under the curve (AUC) value of 0.74. Moreover, in T1 CRC patients after endoscopic resection, miR-195-5p and miR-221-3p were able to predict LNM with an AUC of 0.74. Plasma miRNA signatures may serve as effective predictors for LNM in T1 CRC both before upfront surgery and after endoscopic resection.
format Article
id doaj-art-252ec98edf7b4b9fab2c412eb7c5c956
institution OA Journals
issn 2058-7716
language English
publishDate 2025-02-01
publisher Nature Publishing Group
record_format Article
series Cell Death Discovery
spelling doaj-art-252ec98edf7b4b9fab2c412eb7c5c9562025-08-20T02:15:06ZengNature Publishing GroupCell Death Discovery2058-77162025-02-011111710.1038/s41420-025-02348-5Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resectionKazuaki Okamoto0Hiroaki Nozawa1Tsuyoshi Ozawa2Yoko Yamamoto3Yuichiro Yokoyama4Shigenobu Emoto5Koji Murono6Kazuhito Sasaki7Mitsuhiro Fujishiro8Soichiro Ishihara9Department of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoDepartment of Gastroenterology, The University of TokyoDepartment of Surgical Oncology, The University of TokyoAbstract After endoscopic resection of T1 colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM), additional surgery is required. However, the actual frequency of LNM based on conventional risk factors is less than 16%. There is a need for biomarkers to identify T1 CRC carrying a high risk of metastasis to avoid unnecessary radical surgery. Based on the comparison of serum miRNA between stage I/II and stage III from a large-scale in silico dataset, we conducted a validation analysis of the selected miRNAs using plasma samples from LNM-positive and LNM-negative T1 CRC patients who underwent endoscopic treatment followed by radical surgery at our hospital. In the validation cohort, the three-miRNA classifiers (miR-195-5p, miR-221-3p, and miR-193b-3p) effectively identified LNM-positive T1 CRC patients who received upfront surgery with an area under the curve (AUC) value of 0.74. Moreover, in T1 CRC patients after endoscopic resection, miR-195-5p and miR-221-3p were able to predict LNM with an AUC of 0.74. Plasma miRNA signatures may serve as effective predictors for LNM in T1 CRC both before upfront surgery and after endoscopic resection.https://doi.org/10.1038/s41420-025-02348-5
spellingShingle Kazuaki Okamoto
Hiroaki Nozawa
Tsuyoshi Ozawa
Yoko Yamamoto
Yuichiro Yokoyama
Shigenobu Emoto
Koji Murono
Kazuhito Sasaki
Mitsuhiro Fujishiro
Soichiro Ishihara
Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
Cell Death Discovery
title Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
title_full Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
title_fullStr Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
title_full_unstemmed Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
title_short Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
title_sort comparative microrna signatures based on liquid biopsy to identify lymph node metastasis in t1 colorectal cancer patients undergoing upfront surgery or endoscopic resection
url https://doi.org/10.1038/s41420-025-02348-5
work_keys_str_mv AT kazuakiokamoto comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT hiroakinozawa comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT tsuyoshiozawa comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT yokoyamamoto comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT yuichiroyokoyama comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT shigenobuemoto comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT kojimurono comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT kazuhitosasaki comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT mitsuhirofujishiro comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection
AT soichiroishihara comparativemicrornasignaturesbasedonliquidbiopsytoidentifylymphnodemetastasisint1colorectalcancerpatientsundergoingupfrontsurgeryorendoscopicresection