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

## TL;DR

This study identifies LIMA1-alpha staining as a biomarker to predict which HPV-negative head and neck cancer patients can be treated with surgery alone, avoiding unnecessary additional therapies.

## Contribution

A novel IHC-based diagnostic assay using LIMA1-alpha to stratify HPV-negative HNSCC patients for surgery-only treatment is introduced.

## Key findings

- LIMA1-alpha IHC outperformed other biomarkers in predicting survival in HPV-negative HNSCC patients.
- LIMA1-negative patients in real-world validation cohorts had no HNSCC-related deaths during follow-up.
- LIMA1 regulates epithelial-mesenchymal transition and HNSCC invasion, linking its expression to poor treatment response.

## 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.

Surgery is a mainstay treatment for head and neck squamous cell carcinoma (HNSCC). However, the clinical challenge is to identify those patients who would benefit from surgery alone and would not require extensive oncological treatments that cause adverse effects. In this work, we have identified a novel immunohistochemical (IHC) staining-based method for identifying HNSCC patients who would benefit from surgery alone.

High LIMA1 expression predicted poor survival among HNSCC patients with no evidence of metastatic cancer at the time of diagnosis.Only antibodies that recognize LIMA1-alpha predicted poor treatment response in surgically treated HNSCC patients.Results were validated across population-validated tissue microarray (PV-TMA) and prospective patient cohorts.In vitro and in vivo studies demonstrated that LIMA1 regulated the expression of epithelial-mesenchymal transition (EMT) and HNSCC invasion.

High LIMA1 expression predicted poor survival among HNSCC patients with no evidence of metastatic cancer at the time of diagnosis.

Only antibodies that recognize LIMA1-alpha predicted poor treatment response in surgically treated HNSCC patients.

Results were validated across population-validated tissue microarray (PV-TMA) and prospective patient cohorts.

In vitro and in vivo studies demonstrated that LIMA1 regulated the expression of epithelial-mesenchymal transition (EMT) and HNSCC invasion.

Surgery is a mainstay treatment for head and neck squamous cell carcinoma (HNSCC). However, the clinical challenge is to identify those patients who would benefit from surgery alone and would not require extensive oncological treatments that cause adverse effects. In this work, we have identified a novel immunohistochemical (IHC) staining-based method for identifying HNSCC patients who would benefit from surgery alone.