Hepatocellular carcinoma (HCC) has a high mortality rate, and early detection of HCC improves patient survival. However, the molecular diagnostic markers for early HCC have not been fully elucidated. The aim of this study was to identify novel diagnostic markers for HCC.

Serum protein profiles of 45 hepatitis C virus infection (HCV)-related HCC patients (HCV-HCC) were compared to 42 HCV-related chronic liver disease patients without HCC (HCV-CLD) and 21 healthy volunteers using the ProteinChip SELDI system. One of the identified proteins was evaluated as a diagnostic marker for HCC in patients with HCV.

Five protein peaks (4067, 4470, 7564, 7929, and 8130 m/z) had p-values less than 1 × 10⁻⁷ and were significantly increased in the sera of HCV-HCC patients compared to HCV-CLD patients and healthy volunteers. Among these proteins, an 8130 m/z peak was the most differentially expressed and identified as the complement component 3a (C3a) fragment. For HCV-HCC and HCV-CLD, the relative intensity of this C3a fragment had the best area under the ROC curve [0.70], followed by des-γ-carboxy prothrombin (DCP) [0.68], lectin-bound alpha fetoprotein (AFP-L3) [0.58] and AFP [0.53] for HCC. A combined analysis of the C3a fragment, AFP and DCP led to a 98% positive identification rate. In addition, the measurable C3a fragment in some HCC patients was not only significantly higher in the year of HCC onset compared to the pre-onset year, but also decreased after treatment.

The 8130 m/z C3a fragment is a potential marker for the early detection of HCV-related HCC.