Dataset Information

MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma.

ABSTRACT:

Background

The metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC).

Methods

mRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comparatively studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Immunohistochemistry was employed to analyze MACC1 expression in 308 clinicopathologically characterized HCC cases. Statistical analyses were applied to derive association between MACC1 expression scores and clinical staging as well as patient survival.

Results

Levels of MACC1 mRNA and protein were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. Significant difference in MACC1 expression was found in patients of different TNM stages (P<0.001). Overall survival analysis showed that high MACC1 expression level correlated with lower survival rate (P = 0.001). Importantly, an inverse correlation between MACC1 level and patient survival remained significant in subjects with early-stage HCC or with normal serum AFP level.

Conclusions

MACC1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.

SUBMITTER: Xie C

PROVIDER: S-EPMC3662710 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma.

Xie Chan C Wu Jueheng J Yun Jingping J Lai Jiaming J Yuan Yunfei Y Gao Zhiliang Z Li Mengfeng M Li Jun J Song Libing L

PloS one 20130523 5

<h4>Background</h4>The metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC).<h4>Methods</h4>mRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comp ...[more]

PMID: 23717574

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Project description:BackgroundLiver cirrhosis is one of the major drivers of hepatocellular carcinoma (HCC). In the present study, we aimed to identify and validate new biomarker for early prediction of HCC development in early-stage cirrhosis patients.MethodsmRNA expression and clinical parameters of GSE63898, GSE89377, GSE15654, GSE14520, and TCGA-HCC cohort and ICGC-HCC cohort were downloaded for analysis. Wilcoxon test was performed to identify DEGs. Univariate and multivariate Cox regression analysis were used to develop the risk signature, and ROC analysis was performed to analyze the predictive accuracy and sensitivity of the risk signature.ResultsThere were 42 DEGs (including 28 upregulated genes and 14 downregulated genes) found in early-stage liver cirrhosis patients before developing HCC from GSE1565442. Then, a risk signature consisting of 8 DEGs could effectively classify early-stage cirrhosis patients into high-risk group with shorter HCC development time and low-risk group with longer HCC development time from GSE15654. Multivariate Cox analysis indicated that the risk signature was an independent prognostic factor for the prediction of HCC development and ROC analysis showed that the signature exhibited good predictive efficiency in predicting 2-, 5-, and 10-year HCC development. Mechanistically, significantly higher proportions of CD8 T cells were found to be enriched in cirrhosis patients with low risk score, and higher CD8 T cells were associated with longer HCC development time. Besides, the signature was an independent prognostic factor for poorer prognosis of early-stage liver cirrhosis patients of GSE15654. Moreover, the signature could also separate HCC patients from healthy controls and was also associated with the poorer prognosis of HCC patients from three HCC cohorts. Finally, we also identified HDAC inhibitors, such as trichostatin A, to be a potential chemopreventive treatment for the prevention of HCC development by targeting risk signature based on CMap analysis.ConclusionA risk signature was developed and validated for early prediction of HCC development, which may be a useful tool to set up individualized follow-up interval schedules.

Project description:Background & aimsα-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations.MethodsWe conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12, and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and Hepatocellular Carcinoma Early Detection Screening (HES) scores. We calculated the area under the receiver operating curve and estimated TPR based on an optimal threshold at a fixed FPR of 10%.ResultsThe analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6%, 73.8%, and 71.4% for all HCC, and 53.8%, 63.3%, and 61.8 % for early HCC within 6, 12, and 24 months, respectively) but an FPR of 21.5% to 22.9%. However, there were no differences in the area under the receiver operating curve among GALAD, HES, AFP-L3, or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4%, 45.2%, and 46.9%) and was not different from HES (36.4%, 40.5%, and 40.8%) or AFP-L3 alone (39.4%, 45.2%, and 44.9%).ConclusionsIn a prospective cohort phase III biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false-positive results. GALAD performance was modest and not different from AFP-L3 alone or HES.

Dataset Information

MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma.

Similar Datasets

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