Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients

Abstract

Hepatocellular carcinoma (HCC) is known for its high rate of recurrence and poor prognosis, which makes it necessary to identify new predictive markers for HCC and to explore the underlying mechanism(s). Emerging evidence suggests that the proteoglycan serglycin (SRGN) might play a crucial role in tumor metastasis. However, currently, the function of SRGN in HCC remains unknown. Here, we evaluated the expression pattern of SRGN in 127 HCC specimens and their adjacent, non-tumorous tissues using immunohistochemical assays. We observed that SRGN was significantly upregulated in HCC tissues. Elevated expression levels of SRGN were detectable in 72/127 (56.7%) of the HCC specimens and in 4/127 (3.1%) of adjacent non-tumorous tissues (p < 0.001). Further correlation analysis demonstrated that the increased expression of SRGN was positively associated with HBV infection, GGT level, vascular invasion, advanced BCLC stage and early recurrence (p < 0.05). Increased SRGN expression correlated with unfavorable prognosis in HCC patients. In multivariate analyses, SRGN expression levels were found to represent an independent predictor for overall survival (p = 0.002) and time to recurrence (p = 0.010) of HCC patients. Furthermore, the elevated expression of SRGN in the HCC tissues was accompanied by elevated levels of vimentin and the absence of E-cadherin. Similarly, the reduced expression of SRGN was accompanied by elevated levels of E-cadherin and the absence of vimentin. E-cadherin and vimentin are well-accepted biomarkers of the epithelial-mesenchymal transition (EMT), and the expression of SRGN might correlate with EMT. Our results demonstrate that the elevated expression of SRGN represents a crucial event in HCC patients that is indicative of poor clinical outcome.