Circulating SDF4 as a Potential Early Detection Biomarker for Pancreatic Cancer

Pancreatic cancer is a highly aggressive malignancy that is often diagnosed at an advanced stage, largely due to the lack of reliable biomarkers for early detection. Stromal cell-derived factor 4 (SDF4), also known as Cab45, is a secreted calcium-binding protein localized to the Golgi apparatus, and has been implicated in various tumor types. However, its clinical relevance in pancreatic cancer remains poorly understood. In this study, we investigated the diagnostic potential of circulating SDF4 levels using data from a hospital-based case-control study in Japan, consisting of 124 patients with pancreatic cancer (stage I-IV) and 125 age- and sex-matched controls. Plasma SDF4 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). SDF4 levels were significantly elevated in pancreatic cancer patients across all stages compared with controls (p < 0.001). Notably, patients with early-stage diseases (stage I and II) already exhibited substantial increases. Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.82 for all stages and 0.81 for early-stage patients, indicating good discriminatory performance, including in potentially resectable disease. These findings suggest that SDF4 is elevated as a result of tumor-related biological activity and may represent a promising blood-based biomarker for pancreatic cancer. Its elevation across both early and advanced stage supports further investigation of SDF4 as a complementary marker to carbohydrate antigen 19-9 (CA19-9). Validation in prospective cohorts and in combination with other biomarkers will be essential to clarify its clinical utility.