Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: Association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, β-catenin mutation, and favorable prognosis
Journal
Clinical Cancer Research
Journal Volume
11
Journal Issue
7
Pages
2568-2575
Date Issued
2005
Author(s)
Abstract
Purpose: Pancreatitis-associated protein (PAP) and regenerating protein 1 α (Reg1A) are up-regulated during the pancreas regeneration. This study is to investigate the clinicopathologic denotation of their expression in hepatocellular carcinoma (HCC). Experimental Design: PAP and REG1A mRNA levels were measured in 265 surgically removed unifocal primary HCCs using reverse transcription-PCR. Results: PAP and REG1A mRNAs were detected in 97 (36.6%) and 55 (20.8%) HCCs, respectively, including 46 with coexpression but in none of the 219 nontumorous livers. HCCs with PAP expression correlated with low-stage tumors without evidence of vascular invasion (P = 0.013) but the REG1A expression did not. By a combination analysis, HCCs with PAP expression alone showed the lowest frequency of p53 mutation (P < 0.036), the highest rates of grade 1 and low-stage tumors (P < 0.007 and P < 0.001, respectively), less frequent early tumor recurrence (P = 0.051), and hence a better 5-year survival (P = 0.044) than groups expressing PAP and REG1A, REG1A alone, and neither PAP or REG1A. Besides, PAP expressing HCCs had significantly frequent β-catenin mutation, regardless of REG1A expression, P < 0.00001. In the subset of HCCs that has no mutations of p53 and β-catenin but showed PAP expression, coexpression of REG1A and PAP was associated with more frequent vascular invasion than PAP expression alone (P < 0.005). Conclusions: These data suggest that PAP expression designate a subset of low-grade, low-stage HCC with frequent β-catenin mutation and hence more favorable prognosis, whereas further genetic or epigenetic alterations, such as p53 mutation and REG1A expression, lead to more advanced HCCs. ? 2005 American Association for Cancer Research.
SDGs
Other Subjects
beta catenin; lithostathine; messenger RNA; pancreatitis associated protein; protein p53; protein reg1a; unclassified drug; adolescent; adult; aged; article; cancer invasion; cancer staging; cancer survival; controlled study; female; gene mutation; histopathology; human; human tissue; liver cell carcinoma; major clinical study; male; priority journal; prognosis; protein expression; protein function; tumor growth; tumor recurrence; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; beta Catenin; Calcium-Binding Proteins; Carcinoma, Hepatocellular; Cytoskeletal Proteins; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Lectins, C-Type; Lithostathine; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Nerve Tissue Proteins; Prognosis; RNA, Messenger; Survival Analysis; Trans-Activators; Tumor Markers, Biological; Tumor Suppressor Protein p53
Type
journal article