title: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a tissue biomarker for detection of early hepatocellular carcinoma in patients with cirrhosis.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors occurring mainly in patients with chronic liver disease. Detection of early HCC is critically important for treatment of these patients.
  
  
  METHODS
  We employed a proteomic profiling approach to identify potential biomarker for early HCC detection. Based on Barcelona Clinic Liver Cancer (BCLC) staging classification, 15 early HCC and 25 late HCC tissue samples from post-operative HCC patients and their clinicopathological data were used for the discovery of biomarkers specific for the detection of early HCC. Differential proteins among cirrhotic, early, and late tissue samples were separated by two-dimensional gel electrophoresis (2-DE) and subsequently identified by mass spectrometry (MS). Receiver operating characteristic (ROC) curves analysis were performed to find potential biomarkers associated with early HCC. Diagnosis performance of the biomarker was obtained from diagnosis test.
  
  
  RESULTS
  Protein spot SSP2215 was found to be significantly overexpressed in HCC, particularly in early HCC, and identified as heterogeneous nuclear ribonucleoprotein K (hnRNP K) by tandem mass spectrometry (MALDI TOF/TOF). The overexpression in HCC was subsequently validated by western blot and immunohistochemistry. ROC curve analysis showed that hnRNP K intensity could detect early HCC at 66.67 % sensitivity and 84 % specificity, which was superior to serum α-fetoprotein (AFP) in detection of early HCC. Furthermore, the diagnosis test demonstrated, when combined with hnRNP K and serum AFP as biomarker panel to detect early HCC at different cut-off value, the sensitivity and specificity could be enhanced to 93.33 % and 96 %, respectively.
  
  
  CONCLUSIONS
  hnRNP K is a potential tissue biomarker, either alone or in combination with serum AFP, for detection of early HCC. High expression of hnRNP K could be helpful to discriminate early HCC from a nonmalignant nodule, especially for patients with liver cirrhosis.
authors: Department of Surgery, Beijing Jishuitan Hospital, the Fourth Clinical Medical College of Peking University, Xicheng District, Beijing, China. guoyantong2008@yahoo.com.cn
authors: Yantong
authors: Y
authors: Guo
authors: Jingming
authors: J
authors: Zhao
authors: Jingtao
authors: J
authors: Bi
authors: Quan
authors: Q
authors: Wu
authors: Xin
authors: X
authors: Wang
authors: Quanyou
authors: Q
authors: Lai
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D040901:Proteomics; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D000509:alpha-Fetoproteins