Race-based differences in serum biomarkers for cancer-associated cachexia in a diverse cohort of patients with pancreatic ductal adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related deaths by 2040, with the highest disease burden expected amongst Non-Hispanic Black patients. One of the most significant predictors of poor outcomes is the presence of cancer-associated cachexia (CCa). Yet, race- and ethnicity-specific biomarkers for early CCa diagnosis are lacking. Methods: We evaluated a panel of candidate biomarkers of CCa in a diverse cohort of patients with pre-treatment serum using multiplex ELISA-based methods. Results: We find that growth/differentiation factor-15 (GDF-15) is associated with cachexia severity, is superior to standard biomarkers at classifying cachexia, and differentiates between non-cachexia and pre-cachexia status, but only among Hispanic/Latinx and non-Hispanic White participants. Furthermore, high GDF-15 levels at diagnosis are associated with a greater weight loss from 3.3% (95%CI = −0.14–6.7) to 8.0% (CI = 5.9–10.1) over the 6 months post-diagnosis. Finally, both ENA-78/CXCL5 and GRO-α/CXCL1 are elevated in non-Hispanic Black individuals in a disease-independent manner (P < 0.001 for both analytes). Conclusions: GDF-15 may be a potential biomarker for “pre-cachexia” in the non-Hispanic White and the Hispanic population, but not non-Hispanic Black individuals. These findings underscore the unmet need to enroll non-Hispanic Black participants in clinical trials for CCa.