Serum levels of variants of transthyretin down-regulation in cholangiocarcinoma

Background: Cholangiocarcinoma (CC) is devastating neoplasm and very few specific biomarkers could be used in clinical diagnosis. A study was taken to,find novel serum biomarkers for CC. Methods: Surface enhanced laser desorption/ionization (SELDI) technology was used to analyze427 serum samples including 56 CCs, 49 hepatobiliary diseases, 269 other cancer control, and 53 healthy individuals. The candidates were isolated and identified by SDS-PAGE, ESI/MS-MS, Western blot, and immunoprecipitation. Liver functions of CC patients were examined and enzyme-linked irnmunosorbent assay (ELISA) of transthyretin (TTR) and CA19-9 were further performed in some sets of serum samples. Results: 13.76,13.88, and 14.04 k m/z peaks in sera were significantly decreased in CC compared with the control groups (P < 0.001). Subsequently, these three peaks were identified as native TTR and its two variants. ELISA assay indicated that TTR levels were consistent with SELDI analysis in CC compared with healthy control and benign diseases of hepatobiliary (P < 0.001). Liver function test levels were obviously elevated for CC patients. TTR combining with CA19-9 to differentiate CC from benign hepatobiliary diseases showed sensitivity and specificity were 98.2% and 100%, respectively. Conclusion: The levels of TTR were significantly down-regulated in sera of CC patients and may be complementary markers of CA19-9 in diagnosis for CC.