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. 2025 Jul 25;3(1):53.
doi: 10.1038/s44276-025-00163-0.

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

Taro Aoyama  1   2 , Fumihiko Kakizaki  1 , Hiroyuki Miyoshi  1 , Masahiro Sonoshita  3 , Hisatsugu Maekawa  2 , Yoshiro Itatani  2 , Kenji Kawada  4 , Ryo Matsusue  5   5 , Iwao Ikai  6 , Koki Moriyoshi  7 , Takaki Sakurai  8 , Kazutaka Obama  2 , Tosiya Shun Sato  9 , Yoshiharu Sakai  10 , Makoto Mark Taketo  11
Affiliations

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

Taro Aoyama et al. BJC Rep. .

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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Conflict of interest statement

Competing interests: MMT has ownership interest in and consultant/advisory board relationship with KyoDiagnostics KK (Kyoto, Japan) that executes patent rights owned by Kyoto University for diagnostic use of TRIO pY2681 antibodies. Other authors have no competing interests. Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsinki. The study protocol involving human samples was approved by the Kyoto University Graduate School and Faculty of Medicine, Ethics Committee as well as the Ethics Committee of Kyoto Medical Center. All participants provided their written informed consent for study participation, including the use of their tissue samples and data analysis (Approval No. G0550, FY 2013-2024).

Figures

Fig. 1
Fig. 1. Immunohistochemical assessment of colorectal cancer specimens using new monoclonal antibody for TRIO pY2681.
a Representative examples of TRIO pY2681 immunostaining with monoclonal or polyclonal antibodies. Original magnification ×40. Scale bar, 50 μm. b Grading criteria for TRIO pY2681 protein assessed by immunohistochemistry. The tumors were classified into four staining grades. Grade 0; No staining in tumor cells. Grade 1; Weak staining in tumor cells. Equal intensity as the background. Grade 2; Moderate staining in tumor cells. Higher intensity than the background. Grade 3; Strong staining in tumor cells. We decided to stratify the colon carcinomas staining into two classes: TRIO pY2681-negative (−) (Grade 0 and 1) or TRIO pY2681-positive (+) (Grade 2 and 3). Original magnification ×40. Scale bar, 50 μm.
Fig. 2
Fig. 2. Kaplan-Meier survival analysis of Kyoto Medical Center (KMC) CRC patients whose tumors had TRIO pY2681 (+) or (−).
a Disease-specific survival (DSS) of patients. b–e The Analysis was stratified by stage. f, Relapse-free survival (RFS) of stage 0–III patients. g, h, The analysis was stratified by stage II (g) or III (h). HR, hazard ratio; 95% CI, 95% confidence interval
Fig. 3
Fig. 3. Kaplan-Meier survival analysis of Kyoto University Hospital (KUHP) CRC patients whose tumors had TRIO pY2681 (+) or (-).
a Disease-specific survival (DSS) of patients. b–e, The Analysis was stratified by stage. f Relapse-free survival (RFS) of stage 0–III patients. g, h The analysis was stratified by stage II (g) or III (h). HR, hazard ratio; 95% CI, 95% confidence interval
Fig. 4
Fig. 4
Forest plot of relapse-free survival (RFS) by TRIO pY2681 of selected subgroups in Kyoto University Hospital (KUHP) cohort. RFS hazard ratio (HR) estimates are displayed based on a Cox proportional hazards model for selected subgroups and plotted on the log scale with 95% CI. pStage pathological Stage, pT pathological T, pN pathological N, V invasion venous invasion, Ly invasion lymphatic invasion
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