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Use of serum CXCL16 to predict liver metastasis and prognosis in colorectal cancer patients.

424 Background: Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In CRC, serum levels of CEA have become well-established prognostic indicators. However, it is not generally accepted as optimal in its prognostic power. The aim of this study was to identify novel and reliable serum prognostic markers.


METHODS
We performed cytokine array to identify novel prognostic serum marker, and CXCL16 was selected. To investigate the relationships between sCXCL16 and clinicopathological findings including survival, the serum levels of CXCL16 in 237 CRC patients and 20 normal volunteers were assessed by enzyme-linked immunosorbent assay. Furthermore, we investigated proliferation, invasion and wound healing assay to investigate the biological role of CXCL16 to colon cancer cell by recombinant CXCL16 exposing to HT-29.


RESULTS
The mean sCXCL16 concentration in patients was significantly higher than that in normal volunteers (p<0.0001). In addition, sCXCL16 levels increased significantly in accordance with the progression of UICC stage classification (p < 0.05). In clinicopathologic findings, sCXCL16 was significantly associated with the presence of lymph node (p=0.019) and the presence of liver metastases (p=0.011). Elevated sCXCL16 level demonstrated a significant association with poor survival, and was an independent risk factor for poor survival. Furthermore, sCXCL16 was an independent marker for predicting liver metastasis (logistic analysis; p=0.0015). In vitro, recombinant CXCL16 promoted epithelial mesencymal transition (EMT) phenotype characterized by impaired E-cadherin and induction of Vimentin. In addition, CXCL16 promoted cell growth, migration and invasion.


CONCLUSIONS
Our data demonstrate that preoperative sCXCL16 level increased in colorectal cancer patients, and that sCXCL16 correlated with liver metastasis, and is an independent prognostic factor for overall survival. Elevated CXCL16 has been proposed as a useful predictive marker for liver metastasis and overall survival in CRC. In vitro, CXCL16/CXCR6 axis might play an importance role in mediating cell survival, migration and invasion by EMT in CRC cell. No significant financial relationships to disclose.