Hepatocyte growth factor, transforming growth factor α, and their receptors as combined markers of prognosis in hepatocellular carcinoma

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 apopto...

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Published in:	Molecular carcinogenesis Vol. 36; no. 3; pp. 130 - 141
Main Authors:	Daveau, Maryvonne, Scotte, Michel, François, Arnaud, Coulouarn, Cédric, Ros, Gilles, Tallet, Yveline, Hiron, Martine, Hellot, Marie-France, Salier, Jean-Philippe
Format:	Journal Article
Language:	English
Published:	New York Wiley Subscription Services, Inc., A Wiley Company 01-03-2003
Subjects:	Aged Apoptosis - genetics Biomarkers, Tumor - analysis Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - surgery cirrhosis Female Gene Expression Regulation Hepatitis C - complications hepatitits C Hepatocyte Growth Factor - genetics Humans liver Liver Cirrhosis - etiology Liver Cirrhosis - pathology Liver Neoplasms - diagnosis Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - surgery Male Middle Aged mRNA level Oncogenes Prognosis Proto-Oncogene Proteins c-met - genetics Receptor, Epidermal Growth Factor - genetics severity Transforming Growth Factor alpha - genetics
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Summary:	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.
Bibliography:	ArticleID:MC10103 ark:/67375/WNG-Q1DKCJWG-V istex:FF594C521A3C30676850972DC1077BBBE084E6B3 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0899-1987 1098-2744
DOI:	10.1002/mc.10103