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PRE- AND POSTOPERATIVE CHARACTERIZATION OF ESTABLISHED AND NOVEL BIOMARKERS IN PATIENTS UNDERGOING HEPATOBILIARY SURGERY
Diego Vicente*, Miguel Patino, Rebecca K. Marcus, Heather Lillemoe, Jean-Nicolas Vauthey, Juan Cata, Thomas Aloia
Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX

Background:
Perioperative inflammation has been demonstrated to impact oncologic outcomes in patients (pts) with primary and metastatic liver malignancy. To identify oncologically-relevant inflammatory biomarkers and the underlying systemic signaling, this study sought to compare levels of a customized biomarker panel between healthy controls and pts before and after resection of liver tumors.
Methods:
Prospectively collected demographic, clinicopathologic and perioperative variables were available for all pts. Plasma levels (pg/mL) of previously studied biomarkers (IL-1b/2/4/5/6/7/8/10/12p70/13/17, MCP-1 IFNg, TNFa, MIP-1b, GM-CSF, G-CSF, VEGF, TGFb1, TGFb2, and TGFb3, CXCL12, CXCL10), and novel biomarkers (Resistin, Omentin-1, sLeptin R, Vaspin, PTX3, Galactin-3, FGF-23, PON-1, FGF-21) were measured in healthy controls and in study pts undergoing liver surgery preoperatively, and on postoperative day (POD)1, POD3, and POD5 using multiplex bead assays. Standard statistics were used to assess relationships between biomarker patterns and clinical variables.
Results:
Previously studied biomarkers demonstrated predictable expression patterns in relation to clinicopathologic factors and perioperative events, however, obesity and preoperative chemotherapy was not associated with postoperative biomarker level alterations. Novel biomarker analysis revealed the following correlations: Compared to controls (n=15), pts with hepatic tumors (n=85) demonstrated elevated baseline Galactin3 (13179 vs. 3413, p<0.01), and PTX3 (1577 vs.148, p<0.01) levels. Compared to preoperative levels, the levels of Omentin-1 declined after surgery (196728 vs. 512230, p<0.01). Pts undergoing major hepatectomy had higher post-operative levels of TGFb (4147 vs. 1464, p<0.01) and PTX3 (22451 vs. 12773, p=0.02). Pts who received red blood cell transfusions had increased postoperative IL-5 levels (22.4 vs. 71.4, p=0.03), and pts with postoperative complications had increased IL-17 (12.7 vs. 72.8, p=0.03) and MCP-1 (341.6 vs. 628.5, p=0.05) levels.

Conclusion:
This combined panel confirmed previously reported perioperative patterns of known biomarker levels. In addition, a novel set of biomarkers with potential oncologic value were observed to correlate with perioperative factors and inflammatory stimuli. These results suggest that a comprehensive biomarker panel could be used to test perioperative interventions aimed at reducing the immunosuppressive inflammatory response to surgical stress.


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