Identification of stromal cell-derived factor 4 as a liquid biopsy-based diagnostic marker in solid cancers

There is a need for serum diagnostic biomarkers to improve the prognosis of solid malignant tumors. Here, we conducted a single-institutional study to evaluate the diagnostic performance of serum stromal cell-derived factor 4 (SDF4) levels in cancer patients. Serum samples were collected from a total of 582 patients with solid cancers including gastric cancer (GC) and 80 healthy volunteers. SDF4 protein levels in sera, and conditioned media or lysates of human GC cell lines were measured by enzyme-linked immunosorbent assay, and those in GC tissue by immunohistochemistry. Serum SDF4 levels were higher in patients with cancer than the healthy control in all cancer type. Regarding GC, serum SDF4 levels distinguished healthy controls from GC patients with the area under the curve value of 0.973, sensitivity of 89%, and specificity of 99%. Serum SDF4 levels were significantly elevated in patient with early stage GC. In immunohistochemistry, the frequency of SDF4-positive GC tumors did not vary significantly between GC stages. The ability of human GC cell lines to both produce and secrete SDF4 was confirmed in vitro. In conclusion, serum SDF4 levels could be a promising candidate for a novel diagnostic biomarker for GC and other malignancies.