Evaluating ABCC1 as a potential prognostic biomarker in laryngeal cancer health outcomes

Background : Overexpression of ABCC1 is associated with poor overall survival across many cancers and has been associated with decrease response to chemotherapy. Our in vivo and in vitro studies have shown that ABCC1 expression is higher in laryngeal squamous cell carcinoma (LSCC) from individuals with African heritage. Here, we further investigate ABCC1 as a potential prognostic and predictive marker in laryngeal cancer health outcomes. Methods: ABCC1 gene expression was assessed in tumor tissue from 32 advanced-stage LSCC patients from differing populations via RT-PCR. Immunohistochemistry (IHC) for ABCC1 protein expression was performed on tissue microarrays (TMAs) generated from 61 paraffin-embedded tissues of advanced stage LSCC from patients of differing heritages. Machine learning based digital pathology software (QuPath) was used to semi-quantitate ABCC1 IHC protein expression as H scores. Age, treatment, self-reported heritage, N stage, tumor histologic grade, and ABCC1 H-scores were evaluated as predictors of patient mortality risk via multivariable Cox proportional hazards (CPH) model. The median Cox risk score (cutoff > 0.971) was used to stratify patients into low and high mortality risk groups. The relationship among the clinical features and ABCC1 in low and high mortality risk groups was explored by Chi Square analysis. Overall survival was assessed using the Kaplan-Meier method. Results : LSCCs from patients with African heritage demonstrated a 2.2-fold elevation in ABCC1 gene expression and higher ABCC1 protein expression (H-score) compared with the reference population (p < 0.05). Controlling for treatment, African heritage patients with low ABCC1 H-scores had a high mortality risk (p < 0.05), and patients from the reference population with metastatic disease and high ABCC1 H-scores had a low mortality risk (p < 0.05). Overall, high-risk patients had significantly worse overall survival (HR = 2.46, 95% CI [1.27-4.74], log rank p < 0.01) and high mortality risk was associated with low ABCC1 H-scores and regional metastatic disease (p < 0.05). Conclusion : Although LSCC patients with African heritage have higher ABCC1 expression compared with the reference population, low ABCC1 H-scores carry a higher mortality risk in this group. LSCC patients from the reference population with high ABCC1 H-scores have reduced mortality risk despite having regional metastatic disease. Future studies will involve exploring mechanistic implications of ABCC1 expression on treatment outcomes across differing heritages.