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Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide and is associated with the high rates of morbidity and mortality. α-fetoprotein (AFP) is common used in diagnosis of HCC; however, a growing body of research is questioning the diagnostic power of AFP. There is, therefore, an urgent need to develop additional novel non-invasive techniques for the early diagnosis of HCC, particularly for patients with AFP-negative [AFP(-)] HCC. Accordingly, in the present study, we employed iTRAQ-based mass spectro-metry to analyze the plasma proteins of subjects with AFP(-) HBV-related HCC, AFP(+) HBV-related HCC and non-malignant cirrhosis. We identified 14 aberrantly expressed proteins specific to the HCC patients, including 10 upregulated and 4 downregulated proteins. We verified C-reactive protein (CRP) overexpression by ELISA and immunohistochemical staining of clinical samples. Per ROC curve analyses, CRP was positive in 73.3% of patients with HBV-related HCC, and CRP overexpression had significant diagnostic power for AFP(-) HBV-related HCC. Furthermore, we found that silencing CRP caused a &gt;2-fold decease in HBV replication. Additionally, we determined that this reduction in HBV replication involved the interferon-signaling pathway. However, silencing CRP also promoted HCC invasion and migration in vitro. In conclusion, we demonstrated that CRP can serve as a diagnostic biomarker for AFP(-) HBV-related HCC.

C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma