TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study
Abstract Transmembrane protease serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease family known to be upregulated in many malignancies. We previously showed that TMPRSS4 may be a prognostic biomarker and therapeutic target for gastric cancer (GC), especially in stage III. In...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-93422-6 |
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| author | Hirofumi Tazawa Shinji Hato Shigefumi Yoshino Shinya Otsuka Atsusi Takeno Kazuhiro Toyota Hiromitsu Moriya Isao Nozaki Koji Tanakaya Hideaki Uchiyama Akihisa Saito Kazuya Kuraoka Takeshi Kato Takahisa Suzuki Hirotaka Tashiro |
| author_facet | Hirofumi Tazawa Shinji Hato Shigefumi Yoshino Shinya Otsuka Atsusi Takeno Kazuhiro Toyota Hiromitsu Moriya Isao Nozaki Koji Tanakaya Hideaki Uchiyama Akihisa Saito Kazuya Kuraoka Takeshi Kato Takahisa Suzuki Hirotaka Tashiro |
| author_sort | Hirofumi Tazawa |
| collection | DOAJ |
| description | Abstract Transmembrane protease serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease family known to be upregulated in many malignancies. We previously showed that TMPRSS4 may be a prognostic biomarker and therapeutic target for gastric cancer (GC), especially in stage III. In this retrospective study conducted at 10 institutions, all 325 patients underwent R0 resection involving D2 lymph node dissection. TMPRSS4 expression was examined using immunohistochemical analysis. TMPRSS4 expression was upregulated in 44.9% of participants. The 5-year overall survival (OS) of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (62.4% vs. 76.4%, respectively; p = 0.0149). Univariate analysis revealed that TMPRSS4 upregulation, tumor size, deeper tumor invasion, lymph node metastasis (N), lymphatic invasion, and tumor stage were significant prognostic factors for OS. Multivariate analysis revealed that N and TMPRSS4 upregulation were significant prognostic factors for OS. The 5-year OS rate was examined in two patient groups: the group with the receiver operating characteristic curve cut-off value ≥ 45% for TS-1 (cancer drug formulation) oral dosage and the group with TS-1 dosage cut-off value < 45%. For the patients in the TS-1 dosage ≥ 45% group, there were significant differences in OS between the TMPRSS4-positive and -negative groups (p = 0.0284): the 5-year OS rates of TMPRSS4-positive and -negative groups were 65.2% and 79.2%, respectively. Our findings suggest that TMPRSS4 overexpression is a useful biomarker for GC, and that an anti-TMPRSS4 antibody may have potential as a novel therapeutic agent. |
| format | Article |
| id | doaj-art-d77c7e1c1eaf47e48dfd0fe47ddc1919 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-d77c7e1c1eaf47e48dfd0fe47ddc19192025-08-20T02:56:06ZengNature PortfolioScientific Reports2045-23222025-03-0115111210.1038/s41598-025-93422-6TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective studyHirofumi Tazawa0Shinji Hato1Shigefumi Yoshino2Shinya Otsuka3Atsusi Takeno4Kazuhiro Toyota5Hiromitsu Moriya6Isao Nozaki7Koji Tanakaya8Hideaki Uchiyama9Akihisa Saito10Kazuya Kuraoka11Takeshi Kato12Takahisa Suzuki13Hirotaka Tashiro14Department of Surgery, NHO Kure Medical Center and Chugoku Cancer CenterDepartment of Gastroenterological Surgery, NHO National Hospital Organization Shikoku Cancer CenterDepartment of Surgery, NHO National Hospital Organization Kanmon Medical CenterDepartment of Surgery, NHO National Hospital Organization Fukuyama Medical CenterDepartment of Surgery, NHO National Hospital Organization Osaka National HospitalDepartment of Gastroenterological Surgery, NHO National Hospital Organization Higashihiroshima Medical CenterDepartment of Surgery, NHO National Hospital Organization Sagamihara National HospitalDepartment of Surgery, NHO National Hospital Organization Okayama Medical CenterDepartment of Surgery, NHO National Hospital Organization Iwakuni Clinical CenterDepartment of Surgery, NHO Fukuokahigashi Medical Center, National Hospital Organization Fukuokahigashi Medical CenterDepartment of Diagnostic Pathology, NHO Kure Medical Center and Chugoku Cancer CenterDepartment of Diagnostic Pathology, NHO Kure Medical Center and Chugoku Cancer CenterDepartment of Surgery, NHO National Hospital Organization Osaka National HospitalDepartment of Surgery, NHO Kure Medical Center and Chugoku Cancer CenterDepartment of Surgery, NHO Kure Medical Center and Chugoku Cancer CenterAbstract Transmembrane protease serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease family known to be upregulated in many malignancies. We previously showed that TMPRSS4 may be a prognostic biomarker and therapeutic target for gastric cancer (GC), especially in stage III. In this retrospective study conducted at 10 institutions, all 325 patients underwent R0 resection involving D2 lymph node dissection. TMPRSS4 expression was examined using immunohistochemical analysis. TMPRSS4 expression was upregulated in 44.9% of participants. The 5-year overall survival (OS) of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (62.4% vs. 76.4%, respectively; p = 0.0149). Univariate analysis revealed that TMPRSS4 upregulation, tumor size, deeper tumor invasion, lymph node metastasis (N), lymphatic invasion, and tumor stage were significant prognostic factors for OS. Multivariate analysis revealed that N and TMPRSS4 upregulation were significant prognostic factors for OS. The 5-year OS rate was examined in two patient groups: the group with the receiver operating characteristic curve cut-off value ≥ 45% for TS-1 (cancer drug formulation) oral dosage and the group with TS-1 dosage cut-off value < 45%. For the patients in the TS-1 dosage ≥ 45% group, there were significant differences in OS between the TMPRSS4-positive and -negative groups (p = 0.0284): the 5-year OS rates of TMPRSS4-positive and -negative groups were 65.2% and 79.2%, respectively. Our findings suggest that TMPRSS4 overexpression is a useful biomarker for GC, and that an anti-TMPRSS4 antibody may have potential as a novel therapeutic agent.https://doi.org/10.1038/s41598-025-93422-6Gastric cancerTransmembrane serine protease 4BiomarkerOverall survivalProgression free survival |
| spellingShingle | Hirofumi Tazawa Shinji Hato Shigefumi Yoshino Shinya Otsuka Atsusi Takeno Kazuhiro Toyota Hiromitsu Moriya Isao Nozaki Koji Tanakaya Hideaki Uchiyama Akihisa Saito Kazuya Kuraoka Takeshi Kato Takahisa Suzuki Hirotaka Tashiro TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study Scientific Reports Gastric cancer Transmembrane serine protease 4 Biomarker Overall survival Progression free survival |
| title | TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| title_full | TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| title_fullStr | TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| title_full_unstemmed | TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| title_short | TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| title_sort | tmprss4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study |
| topic | Gastric cancer Transmembrane serine protease 4 Biomarker Overall survival Progression free survival |
| url | https://doi.org/10.1038/s41598-025-93422-6 |
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