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Hepatocyte growth factor, transforming growth factor α, and their receptors as combined markers of prognosis in hepatocellular carcinoma
Author(s) -
Daveau Maryvonne,
Scotte Michel,
François Arnaud,
Coulouarn Cédric,
Ros Gilles,
Tallet Yveline,
Hiron Martine,
Hellot MarieFrance,
Salier JeanPhilippe
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10103
Subject(s) - biology , hepatocellular carcinoma , epidermal growth factor receptor , epidermal growth factor , gdf15 , cirrhosis , cancer research , growth factor , transforming growth factor , receptor , hepatocyte nuclear factor 4 , apoptosis , hepatocyte growth factor receptor , terminal deoxynucleotidyl transferase , hepatocyte , immunohistochemistry , growth factor receptor , hepatocyte growth factor , medicine , endocrinology , tunel assay , immunology , c met , gene , transcription factor , nuclear receptor , biochemistry , in vitro
A change in the balance between proliferation and apoptosis in the course of hepatocellular carcinoma (HCC) development and progression has been suspected. We wanted to identify related genes whose mRNA levels could provide markers of severity and prognosis after resection. The extent of cell apoptosis, proliferation, and differentiation was measured with a terminal deoxynucleotidyl transferase–mediated deoxyuridine 5‐triphosphate–biotin nick‐end labeling assay, and the Ki‐67 index was determined in paired tumor and cirrhotic tissue samples from patients who had undergone HCC resection after diagnosis of hepatitis C–related or alcoholism‐related cirrhosis. These patients included two groups with highly versus poorly differentiated tumor cells, and the latter was split into two subgroups of those with versus without early recurrence. The mRNA levels for various apoptosis‐related or proliferation‐related genes and those for the growth factor/receptor systems were measured by quantitative reverse transcriptase–polymerase chain reaction in paired tumor and cirrhotic liver samples from every patient, and some of the corresponding proteins were detected by immunohistochemistry. In all instances, protein expression was highly heterogeneous within groups and similar between groups. In contrast, some differences in mRNA level between tumor and cirrhotic tissues were quite informative. Low levels of hepatocyte growth factor and transforming growth factor α mRNAs were found concomitantly in highly differentiated tumors, whereas overexpression of mRNAs for the cognate receptors c‐met and epidermal growth factor receptor were found in poorly differentiated tumors and primarily in patients with early tumor recurrence. These results argue for growth factor–dependent HCC development and provide novel and combined prognosis markers after HCC surgery. © 2003 Wiley‐Liss, Inc.