title: C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma.
abstract: 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 >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.
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: She
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ran
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000821:virology*; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000097:blood / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000821:virology*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D012372:ROC Curve; D014779:Virus Replication; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000172:deficiency*
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D002097:C-Reactive Protein