title: Caspase-Cleaved Cytokeratin 18 Fragment M30 as a Potential Biomarker of Macrovascular Invasion in Hepatocellular Carcinoma.
abstract: OBJECTIVE
  Extremely poor prognosis in hepatocellular carcinoma (HCC) patients with progressing disease was denoted by vascular invasion. Cytokeratin 18 (CK18) has been shown to be overexpressed in hepatocellular carcinoma so it is a valuable tumor marker; however, its role in vascular invasion is still unclear. This study aimed to predict CK18 as a predictive marker for macrovascular malignant invasion.
  
  
  METHODS
  The present study was conducted on three groups of patients: group I included 91 HCC patients without macrovascular invasion, group II included 34 HCC patients with radiological evidence of vascular invasion, and group III included 110 control individuals subdivided into IIIA as healthy blood donors and IIIB as post-HCV cirrhotic patients without HCC.
  
  
  RESULTS
  ROC curve of M30 fragments of CK18 was constructed for discrimination between HCC with and without macrovascular invasion. Optimum cutoff value was 304.5 ng/mL (AUC = 0.997, P < 0.001), sensitivity (100%) and specificity (98.8%). Regression analysis was conducted for prediction of macrovascular invasion within HCC patients. The following variables: higher levels of AST, M30, bilirubin, and AFP, lower levels of serum albumin, larger tumor size, child B score, and multiple lesions were associated with vascular invasion in univariate analysis. While in multivariate analysis, higher levels of AST and bilirubin and elevated levels of M30 and AFP serum were considered independent predictors for macrovascular invasion in HCC patients.
  
  
  CONCLUSIONS
  The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.
authors.affiliation: Endemic Medicine Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt. elalfy_hatem66@yahoo.com.
authors.forename: Hatem
authors.initials: H
authors.lastname: Elalfy
authors.affiliation: Endemic Medicine Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Tarek
authors.initials: T
authors.lastname: Besheer
authors.affiliation: Endemic Medicine Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Mona M
authors.initials: MM
authors.lastname: Arafa
authors.affiliation: Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mona Abo-Bakr
authors.initials: MA
authors.lastname: El-Hussiny
authors.affiliation: Radiological Diagnosis Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mahmoud Abd
authors.initials: MA
authors.lastname: El Latif
authors.affiliation: Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Sahar Alsayed Mohamed
authors.initials: SAM
authors.lastname: Alsayed
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000175:diagnosis* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; D010446:Peptide Fragments; D020169:Caspases
keywords: CK18; HCV cirrhotic; Hepatocellular carcinoma; Prognostic value; Tumor biomarker; Vascular invasion