(608) Circulating GDF15 Levels in Oral Cavity Squamous Cell Carcinoma: A Prospective Pilot Cohort Study

Introduction: Oral cavity squamous cell carcinoma (OCSCC) is associated with cancer-related cachexia, yet no unified treatment exists of cancer-related cachexia and treatment targets largely remain in the pre-clinical phase. Growth differentiation factor-15 (GDF15), a stress-response cytokine implicated in cancer-associated anorexia/cachexia, may represent a clinically actionable circulating biomarker in OCSCC as identified in murine models, though human data remains limited.

Methods: This subgroup analysis includes OCSCC patients from an ongoing prospective pilot cohort at a tertiary care center (2022–2024). Eligible subjects were adults (>18 years) with OCSCC treated with upfront surgical resection and pre-operative blood collection on the morning of surgery following informed consent. Circulating GDF15 was evaluated in relation to clinicopathologic tumor characteristics, demographics, and preoperative weight loss, and compared to age-matched healthy controls.

Results: Circulating GDF15 levels were markedly elevated in OCSCC patients (N=22) compared with age-matched healthy controls (N=42) (p < 0.0001). GDF15 levels also trended higher among patients presenting with advanced primary tumor stage and nodal disease, although this association did not reach statistical significance (p=0.053). Additionally, serum GDF15 demonstrated a positive, non-significant correlation with preoperative weight loss (p=0.058).

Conclusions: In this prospective pilot cohort subgroup analysis (N=22), serum GDF15 was significantly elevated in OCSCC relative to age-matched controls, supporting its potential role as a biomarker in this population. However, associations between GDF15 and tumor stage, nodal stage, and pre-treatment weight loss did not reach statistical significance, and should be considered hypothesis-generating. Larger prospective studies are warranted to determine whether GDF15 can support risk stratification and early cachexia-directed intervention.