LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer
Abstract In many solid cancer types, surgery alone could be a sufficient first therapy option for a significant number of cancer patients. However, there are currently no diagnostic solutions to identify patients who could be stratified to surgery alone. To identify a biomarker predicting cancer sur...
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Springer Nature
2025-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00266-8 |
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| author | Xi Qiao Johannes Routila Mari Tienhaara Heikki Irjala Priyadharshini Parimelazhagan Santhi Teemu Huusko Linda Nissi Ilkka Paatero Noora Lehtinen Juha Rantala Toni Viljanen Ilmo Leivo Petri Koivunen Anna Jouppila-Mättö Rami Taulu Leif Bäck Tommy Wilkman Eeva Haapio Ilpo Kinnunen Kari Kurppa Jukka Westermarck Sami Ventelä |
| author_facet | Xi Qiao Johannes Routila Mari Tienhaara Heikki Irjala Priyadharshini Parimelazhagan Santhi Teemu Huusko Linda Nissi Ilkka Paatero Noora Lehtinen Juha Rantala Toni Viljanen Ilmo Leivo Petri Koivunen Anna Jouppila-Mättö Rami Taulu Leif Bäck Tommy Wilkman Eeva Haapio Ilpo Kinnunen Kari Kurppa Jukka Westermarck Sami Ventelä |
| author_sort | Xi Qiao |
| collection | DOAJ |
| description | Abstract In many solid cancer types, surgery alone could be a sufficient first therapy option for a significant number of cancer patients. However, there are currently no diagnostic solutions to identify patients who could be stratified to surgery alone. To identify a biomarker predicting cancer surgery response, candidate biomarkers were studied in a non-metastatic head and neck squamous cell carcinoma (nmHNSCC) cohort well representative of the HPV-negative patient population. LIMA1 immunohistochemistry (IHC) with specificity-validated antibodies outperformed all other biomarkers in multivariable survival analyses of patients with nmHNSCC (n = 128, HR 2.10, P = 0.006). The prognostic effect was selective to LIMA1-alpha isoform IHC detection in patients who had received surgical therapy (n = 184, HR 2.39, P > 0.001). Strikingly, our real-world validation results, using two prospectively collected cohorts (n = 15 and n = 86), demonstrate that none of the LIMA1 negative patients died of HNSCC during the follow-up. Collectively, we report here the discovery of a diagnostic LIMA1-alpha IHC assay for HPV-negative HNSCC patient stratification to surgery-only therapy. Application of LIMA1 detection in routine nmHNSCC diagnostics would revolutionize the clinical management of HNSCC patients. |
| format | Article |
| id | doaj-art-42db8b7e332543b98e91a8b25f7d89b7 |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-42db8b7e332543b98e91a8b25f7d89b72025-08-20T03:42:52ZengSpringer NatureEMBO Molecular Medicine1757-46842025-07-011782095211410.1038/s44321-025-00266-8LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancerXi Qiao0Johannes Routila1Mari Tienhaara2Heikki Irjala3Priyadharshini Parimelazhagan Santhi4Teemu Huusko5Linda Nissi6Ilkka Paatero7Noora Lehtinen8Juha Rantala9Toni Viljanen10Ilmo Leivo11Petri Koivunen12Anna Jouppila-Mättö13Rami Taulu14Leif Bäck15Tommy Wilkman16Eeva Haapio17Ilpo Kinnunen18Kari Kurppa19Jukka Westermarck20Sami Ventelä21Turku Bioscience Centre, University of Turku and Åbo Akademi UniversityDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalInstitute of Biomedicine, and MediCity Research Laboratories, University of TurkuDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalTurku Bioscience Centre, University of Turku and Åbo Akademi UniversityDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalTurku Bioscience Centre, University of Turku and Åbo Akademi UniversityMisvik Biology LtdMisvik Biology LtdDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalDepartment of Pathology, Turku University HospitalDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Oulu and Oulu University HospitalDepartment of Otorhinolaryngology, Head and Neck Surgery, Kuopio University HospitalDepartment of Otorhinolaryngology, Head and Neck Surgery, Tampere University Hospital and University of TampereDepartment of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University HospitalDepartment of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University HospitalDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalDepartment for Otorhinolaryngology, Head and Neck Surgery, University of Turku and Turku University HospitalInstitute of Biomedicine, and MediCity Research Laboratories, University of TurkuTurku Bioscience Centre, University of Turku and Åbo Akademi UniversityTurku Bioscience Centre, University of Turku and Åbo Akademi UniversityAbstract In many solid cancer types, surgery alone could be a sufficient first therapy option for a significant number of cancer patients. However, there are currently no diagnostic solutions to identify patients who could be stratified to surgery alone. To identify a biomarker predicting cancer surgery response, candidate biomarkers were studied in a non-metastatic head and neck squamous cell carcinoma (nmHNSCC) cohort well representative of the HPV-negative patient population. LIMA1 immunohistochemistry (IHC) with specificity-validated antibodies outperformed all other biomarkers in multivariable survival analyses of patients with nmHNSCC (n = 128, HR 2.10, P = 0.006). The prognostic effect was selective to LIMA1-alpha isoform IHC detection in patients who had received surgical therapy (n = 184, HR 2.39, P > 0.001). Strikingly, our real-world validation results, using two prospectively collected cohorts (n = 15 and n = 86), demonstrate that none of the LIMA1 negative patients died of HNSCC during the follow-up. Collectively, we report here the discovery of a diagnostic LIMA1-alpha IHC assay for HPV-negative HNSCC patient stratification to surgery-only therapy. Application of LIMA1 detection in routine nmHNSCC diagnostics would revolutionize the clinical management of HNSCC patients.https://doi.org/10.1038/s44321-025-00266-8EPLINDisease-Specific SurvivalPopulation-validated Tissue MicroarrayPV-TMA |
| spellingShingle | Xi Qiao Johannes Routila Mari Tienhaara Heikki Irjala Priyadharshini Parimelazhagan Santhi Teemu Huusko Linda Nissi Ilkka Paatero Noora Lehtinen Juha Rantala Toni Viljanen Ilmo Leivo Petri Koivunen Anna Jouppila-Mättö Rami Taulu Leif Bäck Tommy Wilkman Eeva Haapio Ilpo Kinnunen Kari Kurppa Jukka Westermarck Sami Ventelä LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer EMBO Molecular Medicine EPLIN Disease-Specific Survival Population-validated Tissue Microarray PV-TMA |
| title | LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer |
| title_full | LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer |
| title_fullStr | LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer |
| title_full_unstemmed | LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer |
| title_short | LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer |
| title_sort | lima1 alpha staining predicts curative intent surgery response in hpv negative head and neck cancer |
| topic | EPLIN Disease-Specific Survival Population-validated Tissue Microarray PV-TMA |
| url | https://doi.org/10.1038/s44321-025-00266-8 |
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