SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma

Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients’ outcome.