Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients

Abstract Background We previously reported that TRIO pY2681, a novel prognostic biomarker for CRC, can be detected by polyclonal antibodies (pAb). We have now developed a novel monoclonal antibody (mAb) that recognizes TRIO pY2681. This study aims to assess the utility of immunohistochemical (IHC) s...

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Main Authors: Taro Aoyama, Fumihiko Kakizaki, Hiroyuki Miyoshi, Masahiro Sonoshita, Hisatsugu Maekawa, Yoshiro Itatani, Kenji Kawada, Ryo Matsusue, Iwao Ikai, Koki Moriyoshi, Takaki Sakurai, Kazutaka Obama, Tosiya Shun Sato, Yoshiharu Sakai, Makoto Mark Taketo
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:BJC Reports
Online Access:https://doi.org/10.1038/s44276-025-00163-0
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author Taro Aoyama
Fumihiko Kakizaki
Hiroyuki Miyoshi
Masahiro Sonoshita
Hisatsugu Maekawa
Yoshiro Itatani
Kenji Kawada
Ryo Matsusue
Iwao Ikai
Koki Moriyoshi
Takaki Sakurai
Kazutaka Obama
Tosiya Shun Sato
Yoshiharu Sakai
Makoto Mark Taketo
author_facet Taro Aoyama
Fumihiko Kakizaki
Hiroyuki Miyoshi
Masahiro Sonoshita
Hisatsugu Maekawa
Yoshiro Itatani
Kenji Kawada
Ryo Matsusue
Iwao Ikai
Koki Moriyoshi
Takaki Sakurai
Kazutaka Obama
Tosiya Shun Sato
Yoshiharu Sakai
Makoto Mark Taketo
author_sort Taro Aoyama
collection DOAJ
description Abstract Background We previously reported that TRIO pY2681, a novel prognostic biomarker for CRC, can be detected by polyclonal antibodies (pAb). We have now developed a novel monoclonal antibody (mAb) that recognizes TRIO pY2681. This study aims to assess the utility of immunohistochemical (IHC) staining using the TRIO pY2681 mAb as a prognostic marker for CRC in clinical practice. Methods IHC using TRIO pY2681 mAb was performed on surgical specimens from 357 CRC patients at Kyoto Medical Center and 320 at Kyoto University Hospital. Based on the results, we conducted a retrospective outcome analysis. Results TRIO pY2681 mAb exhibited significantly higher titers than pAb. In both cohorts of all stages, TRIO pY2681 IHC positivity correlated with shorter disease-specific survival (DSS) (HR, 1.67; 95% CI, 1.00–2.79; P = 0.046, and HR, 5.84; 95% CI, 2.26–15.1; P < 0.001) and relapse-free survival (RFS) (HR, 1.92; 95% CI, 1.15–3.22; P = 0.011, and HR, 4.36; 95% CI, 2.17–8.76; P < 0.001). The trend persisted in stage III. Multivariate analysis confirmed TRIO pY2681 IHC positivity as an independent prognostic factor for RFS. Conclusions The novel TRIO pY2681 mAb identifies CRC patient subsets with poorer prognoses, enhancing prognostic precision in clinical settings.
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spelling doaj-art-8180abe2606b446ea8a14c347c2a2e472025-08-20T04:01:53ZengNature PortfolioBJC Reports2731-93772025-07-01311810.1038/s44276-025-00163-0Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patientsTaro Aoyama0Fumihiko Kakizaki1Hiroyuki Miyoshi2Masahiro Sonoshita3Hisatsugu Maekawa4Yoshiro Itatani5Kenji Kawada6Ryo Matsusue7Iwao Ikai8Koki Moriyoshi9Takaki Sakurai10Kazutaka Obama11Tosiya Shun Sato12Yoshiharu Sakai13Makoto Mark Taketo14Colon Cancer Project, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto UniversityColon Cancer Project, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto UniversityColon Cancer Project, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto UniversityDivision of Biomedical Oncology, Institute for Genetic Medicine, Hokkaido UniversityDepartment of Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Surgery, Kurashiki Central HospitalDepartment of Gastroenterological Surgery, Tenri HospitalDepartment of Surgery, Koseikai Takeda HospitalDepartments of Diagnostic Pathology, Kyoto Medical Center, National Hospital OrganizationDepartment of Pathology, Japanese Red Cross Osaka HospitalDepartment of Surgery, Graduate School of Medicine, Kyoto UniversityInstitute of Statistical Mathematics, and Data Science and AI Innovation Research Promotion Center, Shiga UniversityDepartment of Surgery, Japanese Red Cross Osaka HospitalColon Cancer Project, Kyoto University Hospital-iACT, Graduate School of Medicine, Kyoto UniversityAbstract Background We previously reported that TRIO pY2681, a novel prognostic biomarker for CRC, can be detected by polyclonal antibodies (pAb). We have now developed a novel monoclonal antibody (mAb) that recognizes TRIO pY2681. This study aims to assess the utility of immunohistochemical (IHC) staining using the TRIO pY2681 mAb as a prognostic marker for CRC in clinical practice. Methods IHC using TRIO pY2681 mAb was performed on surgical specimens from 357 CRC patients at Kyoto Medical Center and 320 at Kyoto University Hospital. Based on the results, we conducted a retrospective outcome analysis. Results TRIO pY2681 mAb exhibited significantly higher titers than pAb. In both cohorts of all stages, TRIO pY2681 IHC positivity correlated with shorter disease-specific survival (DSS) (HR, 1.67; 95% CI, 1.00–2.79; P = 0.046, and HR, 5.84; 95% CI, 2.26–15.1; P < 0.001) and relapse-free survival (RFS) (HR, 1.92; 95% CI, 1.15–3.22; P = 0.011, and HR, 4.36; 95% CI, 2.17–8.76; P < 0.001). The trend persisted in stage III. Multivariate analysis confirmed TRIO pY2681 IHC positivity as an independent prognostic factor for RFS. Conclusions The novel TRIO pY2681 mAb identifies CRC patient subsets with poorer prognoses, enhancing prognostic precision in clinical settings.https://doi.org/10.1038/s44276-025-00163-0
spellingShingle Taro Aoyama
Fumihiko Kakizaki
Hiroyuki Miyoshi
Masahiro Sonoshita
Hisatsugu Maekawa
Yoshiro Itatani
Kenji Kawada
Ryo Matsusue
Iwao Ikai
Koki Moriyoshi
Takaki Sakurai
Kazutaka Obama
Tosiya Shun Sato
Yoshiharu Sakai
Makoto Mark Taketo
Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
BJC Reports
title Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
title_full Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
title_fullStr Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
title_full_unstemmed Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
title_short Monoclonal antibody for phosphorylated TRIO Y2681 that helps predict prognosis of post-operative colorectal cancer patients
title_sort monoclonal antibody for phosphorylated trio y2681 that helps predict prognosis of post operative colorectal cancer patients
url https://doi.org/10.1038/s44276-025-00163-0
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