LIMA1-alpha staining predicts curative intent surgery response in HPV negative head and neck cancer

    Authors: 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

    Journal: EMBO Molecular Medicine

    Year: 2025

    DOI: https://doi.org/10.1038/s44321-025-00266-8

    Abstract

    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.