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PLASMA LEVELS OF CLCL16 ARE SIGNIFICANTLY INCREASED IN PATIENTS WITH COLORECTAL CANCER COMPARED TO BENIGN DISEASE COLON PATHOLOGY
H M C Shantha Kumara*1, Sandhu K. Jaspreet1,2, Carl Winkler1, Simon Tian1, Abhinit Shah1, Xiaohong Yan1, Hiromichi Miyagaki1,3, Vesna Cekic1, Nipa D. Gandhi1, Richard L. Whelan1
1Surgery, Mount Sinai West Hospital, New York, NY; 2Surgery,, Brookdale Hospital Medical Center, New York, NY; 3Surgery, Saiseikai Senri Hospital, Osaka-565-0862, 1-1-6, Tsukumodai, Suita, Japan
Introduction: Transmembrane chemokine CXCL16 is a member of the chemokine super family, and its activity likely results from a soluble form shed from the membrane. CXCL16 is primarily expressed on the surface of leukocytes, endothelial cells(EC) and by many other organs. Its receptor, CXCR6, is found on cells at sites of inflammation. CXCL16 and CXCR6 are a ligand-receptor pair thought to be associated with endothelial precursor cell recruitment and angiogenesis in response to pro-inflammatory stimuli. CXCL16/CXCR6 signaling mediates cancer cell progression via pERK1/2 and AKT/mTOR signaling pathway in certain malignancies. CXCL16 is expressed constitutively in primary cancers including prostate, melanoma and colorectal cancer (CRC). Plasma levels of CXCL16 in colorectal CRC patients (pts) have not been well studied. This study's purpose was to compare preoperative (PreOp) plasma CXCl16 levels in CRC and benign colonic pathology (BCP) patients.
Method: Preoperative (PreOp) plasma samples of CRC and BCP pts who underwent elective resection were obtained from an IRB approved data/plasma bank. Clinical, demographic and final pathological data were reviewed. Plasma CXCL16 levels were determined via ELISA in duplicate and are reported as median ±95% CI (ng/ml). Expression levels were determined in tumors and paired normal tissues of a subpopulation of study patients by QRT-PCR .The candidacy of CXCL16 as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Mann-Whitney test was used for statistical analysis, (significance(sig) p<0.05).
Results: A total of 106 CRC (71%colon, 29%rectal) and 102 BCP patients (adenoma 45%, diverticulitis 43%, other 12%) were studied. The male/female ratios were similar but the CRC patients were older (p<0.0001). The CRC stage distribution was: Stage 1, 30%; Stage 2, 30%; Stage 3, 35%; and Stage 4, 5%. The median plasma CXCL16 levels were significantly higher in the CRC (2.33 CI 2.16, 2.54) vs. the BCP patients (1.98 CI 1.87, 2.03; P=< 0.001). 35 % of the CRC tumors tested (8/23) showed elevated CXCL16 expression vs. paired normal tissue. ). The AUC value for ROC curve was 0.772(sensitivity 46%, specificity 57%).
Conclusion: The CRC median CXCL16 level was 18% higher than the BCP result and 11-27% (non -significant) higher in STG 4 vs. STG I,II and III patients. In general, plasma CXCL16 levels increased with advancing cancer stage. The AUC results suggest CXCL16 in combination with other CRC maker protein may have value as a CRC prognostic marker. The most likely source of the added CXCL16 in the plasma is the tumor and inflammatory lymphocytes. Further study with larger populations of control and CRC pts is warranted.
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