Abstract 798: The genetic link between psychosocial stress and outcome in oral squamous cell carcinoma

Abstract Psychological well-being predicts future physical health and mortality beyond its association with reduced stress and depression. Studies on psychological well-being in cancer have not evaluated the effect of psychosocial stressors on cancer outcomes. The objective of this study was to investigate the impact of psychosocial stressors and their resultant dysregulated genetic pathways on oral squamous cell carcinoma (OSCC) outcomes. This prospective multi-institutional study enrolled 173 OSCC patients to determine prior and current psychosocial stressors (using the Adverse Childhood Experience - ACE and Life Events Checklist - LEC-5), characterize cancer symptoms and quality of life disturbance (using the UCSF Oral Pain Questionnaire - UCSF-OPQ, modified Brief Pain Inventory - BPI, and EORTC-QLQC30 and H&N35), and collect flash-frozen cancer tissue for RNA-sequencing. Data was analyzed by a biostatistician using Pearson correlation, Student's t-test, one-way ANOVA, Kaplan Meier log-rank test and Cox hazard regression. Our cohort consisted of 99 males, 74 females; racial/ethnic composition included 118 White, 14 Asian, 12 Black, and 28 White-Hispanic. The mean age of the cohort was 64. Patients who had high cancer pain (UCSF-OPQ) had significantly greater physical and psychological interferences (modified BPI; p<0.05). Patients with worse pain also had disturbances in all 6 functional categories measured by EORTC-QLQC30, including physical functioning, role functioning, emotional functioning, cognitive function, social functioning, and global health status (p<0.0001). In terms of the effect of childhood or adult psychosocial stressors on cancer outcomes, patients with a high ACE or LEC-5 score had worse cancer symptoms (in all symptom scales including modified BPI, EORTC-QLQ, and H&N35) independent of their pathologic stage. A Cox hazard regression model showed that the H&N35 score (HR = 1.969, CI 95% [1.060 - 3.659]) was independent of pathologic stage (HR =1.808, CI 95% [1.244-2.628] and age (HR: 1.669, CI 95% [1.151-2.419]) in predicting survival. Analysis of RNA-seq data in flash-frozen cancer tissue of 50 OSCC patients showed that the extracellular matrix organization and the regulation of integrin-mediated signal pathways were dysregulated in patients with high pain levels. Additionally, patients with psychosocial stress exhibited high expression of genes such as RLP6, RPL11, and RPL23, which are known to play significant roles in lung and gastric cancer but not previously associated with OSCC. Enriched pathways in these patients included ribonucleoprotein complex biogenesis and regulation of p53-mediated signal transduction. Our results demonstrate that psychosocial stressors worsen cancer symptoms, which is independently associated with worse cancer outcomes and survival. We delineate the significant dysregulated pathways linking behavioral health to cancer outcomes. Citation Format: Minh Phuong Dong, Gary Yu, Michele Arambula, Bradley Aouizerat, Khanh Nguyen, Paul Walker, Carissa Thomas, Chi Viet. The genetic link between psychosocial stress and outcome in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 798.