Transcript AA454543 Is a Novel Prognostic Marker for Hepatocellular Carcinoma after Curative Partial Hepatectomy

Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
Neoplasia (Impact Factor: 4.25). 02/2005; 7(2):91-8. DOI: 10.1593/neo.04472
Source: PubMed


We have previously reported on the cDNA microarray gene expression profiles of hepatocellular carcinomas (HCCs). Among the genes that show prognostic significance and are overexpressed in tumor compared with adjacent nontumorous liver, transcript AA454543 may have potential for practical use. Our aim is to validate the prognostic significance of transcript AA454543 by alternative research methods and in a separate group of HCC patients.
The data of transcript AA454543 derived from microarray analysis of 48 patients having curative partial hepatectomy (group 1) were verified by quantitative reverse transcription polymerase chain reaction (r = 0.618, P < .001). A separate sample set of HCCs obtained from 53 patients (group 2) was examined and the association of AA454543 expression level with overall survival was again validated (P = .027). By Cox regression analysis, transcript AA454543 [hazard ratio (HR) = 3.0, P = .017] and pathologic tumor node metastasis (pTNM) stage (HR = 3.3, P = .010) were independent prognostic factors for overall survival. The accuracy of prediction for 3-year overall survival for transcript AA454543 (74.2%, P = .001) and pTNM stage (76.4%, P = .001) was comparable as measured by the area under the receiver operating characteristic curve.
Transcript AA454543 is potentially useful molecular prognostic marker for overall survival after curative partial hepatectomy for HCC.

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    • "Such factors might be preoperatively determined tumor-related cell-free nucleic acids in plasma and serum. Recently, the preoperative plasma transcript AA454543 level has been identified as a prognostic parameter in hepatocellular carcinoma [6] [7]. However, such novel and promising prognostic markers are still based on the presence of tumor mass. "
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    ABSTRACT: The GNAS1 locus encodes the Galphas protein, which stimulates the formation of cyclo-adenosinemonophosphate (cAMP). The cAMP pathway mediates pleiotropic effects, including the regulation of apoptosis and proliferation. We have recently shown that TT genotypes of the single-nucleotide polymorphism T393C in the gene GNAS1 predict the clinical outcome of patients with various carcinomas. Eighty-seven patients with intrahepatic cholangiocarcinoma (ICC) were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome. ICCs of patients with homozygous TT genotypes revealed a higher proliferation rate and a lower apoptotic rate. Homozygous TT patients were at highest risk for cancer-related deaths (hazard ratio = 2.74; 95% confidence interval = 1.03-7.28) compared with C-allele carriers. Kaplan-Meier curves for disease-specific overall and local recurrence-free survival in a subgroup with R(0)-resected ICC showed a significant association of T393 homozygosity with outcome, which was confirmed in multivariate Cox regression analysis. GNAS1 T393C is a novel independent host factor for disease progression in patients with ICC. Our finding that TT homozygosity (and not CC homozygosity) was associated with unfavorable clinical outcome points to the complex and differing functional effects induced by GNAS1 T393C polymorphism in various human carcinomas.
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    • "Importantly, transcript AA45453 levels in tumor tissues and tumor stage were independent prognostic factors for overall survival [12]. The prognostic significance of transcript AA454543 was first identified in our earlier cDNA microarray dataset [11], in which data were validated by quantitative reverse transcription – polymerase chain reaction (RT-PCR) and then confirmed in a separate HCC sample set [12]. Thus, quantitative assay of the molecular marker transcript AA454543 in tumor tissues can provide general prognostic information (two independent cohorts of HCC patients, and prediction is independent of the assay method used). "
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    ABSTRACT: We have previously reported that tissue expression levels of transcript AA454543 in hepatocellular carcinoma (HCC) are significantly higher than those of normal livers, livers with cirrhosis, and livers with hepatitis. In addition, a higher level of transcript AA454543 in tumor tissues is associated with poor prognosis. We aim to examine whether quantitative measurement of preoperative plasma transcript AA454543 can provide similar prognostic information. Blood samples were obtained from 84 HCC patients before surgery. Real-time quantitative reverse transcription-polymerase chain reaction, using TaqMan system, was employed to measure plasma transcript AA454543 and alpha-fetoprotein (AFP) RNA levels. We assessed their prediction power in prognosis using univariate and multivariate analyses. High plasma transcript AA454543 RNA levels were associated with poor overall survival (log-rank test, P < .01). Patients with different plasma AFP RNA levels revealed no difference in overall survival (log-rank test, P = .88). By multivariate Cox regression analysis, plasma transcript AA454543 RNA level (hazard ratio = 4.8, P < .01) and tumor stage (hazard ratio = 1.7, P < .01) were determined to be independent risk factors for the prediction of overall survival. Preoperative plasma transcript AA454543 RNA level can provide prognostic information for HCC patients receiving curative partial hepatectomy.
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