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Kan-1 (Bile acid CoA:Amino acid N-acyltransferase) messenger RNA as a novel predictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy

✍ Scribed by M Furutani; S Arii; H Higashitsuji; M Mise; M Niwano; T Harada; H Nakayama; M Fukumoto; M Imamura; J Fujita


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
305 KB
Volume
24
Category
Article
ISSN
0270-9139

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✦ Synopsis


Hepatocellular carcinoma (HCC) is one of the most common

We identified kan-1 complementary DNA (cDNA), the cancers in the Orient and in South Africa. Over the past 10 sequence of which is identical to bile acid CoA:amino years, great progress has been made in the diagnosis and acid N-acyltransferase (BAT), a liver enzyme that catatreatment of HCC patients, and consequently, the number lyzes the conjugation of bile acids with glycine or tauof resectable cases has increased. 3,4 However, despite this rine. Kan-1(BAT) messenger RNA (mRNA) levels of the remarkable progress, the survival rate remains poor. One of resected specimens obtained from 37 hepatocellular carthe major barriers to the attainment of longer survival seems cinoma (HCC) patients were studied in an attempt to to be intrahepatic recurrence even after total removal of the evaluate prognostic significance in HCC patients after tumor macroscopically. 5,6 In this regard, great effort has been partial hepatectomy. Using Northern blot hybridization, given to determining the predictive factors affecting intrahekan-1(BAT) mRNA levels were quantified in tumorous patic recurrence and long-term survival. New molecular and nontumorous tissues, and the ratio of the former to markers that add predictive value to the conventional clinical the latter was defined as the kan-1(BAT) ratio. Twelve predictive factors, such as portal involvement, a-fetoprotein patients had a kan-1(BAT) ratio õ 0.

5 (low kan-1[BAT]

(AFP) level, tumor size, number of tumors, are still deratio), and 25 patients had a ratio ú0.5 (high kan-1[BAT] sired. 4,5,[7][8][9] In this context, the present study was designed to ratio). The patients with a low kan-1(BAT) ratio demonevaluate the prognostic significance of the expression of the strated poorer survival than the patients with a high kan-1(BAT) gene in HCC patients after curative resection.

kan-1(BAT) ratio (P Å .0013). The overall estimated haz-

Evidence will be presented to demonstrate that kan-1(BAT) ard ratio for death in patients with a low kan-1(BAT) mRNA level is a novel molecular marker for estimating progratio was 68.05 according to a multivariate model (P Å nosis and for differentiating HCC from other liver tumors, .0005). Thus, the kan-1(BAT) ratio may serve as a new and the rationale for this conclusion will be discussed. molecular prognostic marker in HCC patients, following hepatic resection. (HEPATOLOGY 1996;24:1441-1445.)

PATIENTS AND METHODS

Study Population. A total of 28 men and 9 women (age range, 39

Recently, we identified a novel gene, kan-1, in the rat liver to 76 years; mean, 61.4 years), whose profiles are listed in Table 1, using an RNA-polymerase chain reaction cloning strategy. 1 were studied. All HCC patients underwent partial hepatic resection at the Kyoto University Hospital, and tumorous and contiguous non-Kan-1 complementary DNA (cDNA) encodes a 46-kd protein, tumorous tissues were collected with the consent of the patients.

Abbreviations: cDNA, complementary DNA; mRNA, messenger RNA; BAT, bile acid amount of kan-1(BAT) mRNA was determined by densitometric scan-CoA:amino acid N-acyltransferase; HCC, hepatocellular carcinoma; AFP, a-fetoprotein.

ning of autoradiograms with an ATTO Densitograph (Tokyo, Japan), From the 1 First Department of Surgery, and the Departments of 2 Clinical Molecular and normalized to S26 ribosomal protein mRNA. The kan-1 (BAT)