Cholangiocarcinoma (CCA) express chemokine receptor CXCR7: Important role of CXCR7 in mediating CXCL12 induced CCA cells chemotaxis and survival

mechanisms that facilitate TGF-b related hepatocarcinogenesis. Methods: With Bioinformatics, we screened 7 published HCC cohorts including 472 patients as compared to normal liver samples or non-tumor surrounding tissue, 21 HCC cell lines, and hepatic stellate cells upon culture activation and from BDL and CCl4 mouse models for expression of candidate TSRs. Results: From 145 genes of our initial TSR list, 85 displayed expression modulation in HCC (39 up-regulated, 46 downregulated). We are now correlating the hits with HCC stages and clinical outcomes. Further, we have setup human and mouse TSR panels to experimentally estimate our findings in our own patients collective (140 HCC patients), genetic (TGF-a/c-Myc, Mdr2ko) and chemical (DEN) mouse models of liver cancer. Most promising candidates with modulated expression in all cohorts comprise BAMBI, BMPER, Dermatopontin, Decorin, SPARC and CD109, which will now be investigated mechanistically in HCC cell lines and myofibroblasts. Conclusions: High-throughput omics technologies have been widely applied and provide large amounts of data. Here we show how these can be used to identify novel candidates for CLD/HCC subclassification, e.g. related to TGF-b signaling.