Prognostic impact of syndecan-1 expression and serum concentration in colorectal cancer

Syndecan-1 (SDC1), a transmembrane heparan sulfate proteoglycan that serves an important role in promoting tumorigenesis and metastasis, has been suggested as a potential biomarker for malignancy and as a therapeutic target. However, its role remains controversial because of its varying functions depending on carcinoma type and location. Elevated serum SDC1 levels after surgery have previously been associated with favorable disease-free survival (DFS). The present study aimed to clarify the role of SDC1 in resectable colorectal cancer (CRC) by evaluating its expression in tumor tissue, correlation with serum SDC1 levels and association with prognosis. In total, 46 patients who underwent radical surgery between July and December 2019 at Gifu University Hospital (Gifu, Japan) were included. The association between SDC1 expression in tumor tissues, assessed using immunohistochemical staining, and DFS was analyzed. Tumor tissue was compartmentalized into the membrane, cytoplasm and stroma. Staining intensity and percentage of positive cells were scored and categorized into two groups based on quartiles (Qs). The Q3-Q4 SDC1 staining scores for the membrane, cytoplasm and stroma were 30 (65.2%), 26 (56.6%) and 23 (50.0%) patients, respectively. Low SDC1 expression in all compartments was associated with advanced tumor stage (P=0.017, P=0.008 and P=0.035). In addition, low membranous SDC1 expression was associated with shorter DFS (P=0.013) and was an independent risk factor for recurrence (hazard ratio: 7.00, 95% confidence interval: 1.24-39.62, P=0.028). No significant correlation was observed between membranous SDC1 expression and serum SDC1 levels. The current study demonstrated that low membranous SDC1 expression may be an independent risk factor for recurrence and could serve as a prognostic biomarker for CRC. Furthermore, serum SDC1 levels may not depend solely on expression in tumor cells and are possibly influenced by multiple factors, including the tumor microenvironment and release from other tissues.