Screening and detection of portal vein tumor thrombi-associated serum low molecular weight protein biomarkers in human hepatocellular carcinoma

Purpose Serum low molecular weight protein biomarkers might be important in relation to portal vein tumor thrombi (PVTT) in hepatocellular carcinoma (HCC). This study aimed to screen and to detect these biomarkers. Methods We selected sera of 3 groups from 12 healthy volunteers, 12 HCC patients without PVTT and 12 HCC patients with PVTT, respectively. By using two-dimensional gel electrophoresis (2-DE) in which the first dimension was 16% SDS-PAGE, serum protein images of 3 groups were analyzed by Image Master Software. The differential protein spots were further identified by MALDI-TOF MS/MS. Results Compared with 12.5% SDS-PAGE gel, there were more protein bands between 3 and 20 kDa in 16% SDS-PAGE gel and low molecular weight (MW) protein spots (<20 kDa) were clearly shown. Fifteen differential protein spots representing five proteins were found in the three groups by inter-class comparison and were then identified. Compared with the healthy group, apolipoprotein A-I, lipoprotein CIII, transthyretin and DNA topoisomerase II were down regulated in HCC groups while haptoglobin-2 was over expressed. All the five proteins were less in PVTT group than in non-PVTT group. Conclusion The expression of low MW serum protein changes obviously in the beginning and progressive stage of HCC, and differentially expressed low MW proteins might be the potential biomarkers in early prognostication and surveillance of treatment for HCC and PVTT.