A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early-Stage Hepatocellular Carcinoma Patients

Abstract

Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5 cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with earlystage tumors and solitary presentation. Cancer Res; 70(24); 10202-12. Ó2010 AACR.

Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma

“…We found that only the isoform a (MPZL1) is overexpressed in HCC compared with adjacent non-tumor tissues (Supplementary information, Figure S2). Consistent with our findings, Oncomine expression analysis also revealed higher MPZL1 expression in HCC tissues than in normal liver tissues in two independent sets of HCC specimens [21,22] (Supplementary information, Figure S3). …”

A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions

“…The gene expression data of the HCC cohort have been published previously (23,24). In brief, gene expression profiling was performed using the National Cancer Institute's Human Array-Ready Oligo Set microarray platform and Affymetrix GeneChip HG-U133A 2.0 arrays, respectively.…”

“…We analyzed gene expression data from a cohort of 195 HCC patients with available survival data (23,24). We found that although diminished expression of single genes or two genes together had no or only moderate association with survival outcome (Fig.…”

Coordination of Nutrient Availability and Utilization by MAX- and MLX-Centered Transcription Networks

“…3) (Basso et al 2005;Detwiller et al 2005;Sanchez-Carbayo et al 2006;Tomlins et al 2007). TXNIP mRNA levels are also generally lower in (Roessler et al 2010) Ovarian serous cystadenocarcinoma (TCGA) Chronic lymphocytic leukemia (Haslinger et al 2004) Thyroid gland oncocytic adenoma (Giordano et al 2006) Ovarian carcinoma (Bonome et al 2008) Cutaneous melanoma (Talantov et al 2005) Tongue squamous cell carcinoma (Talbot et al 2005) Colon adenocarcinoma ( 1.55E-7…”

“…3) (Bhattacharjee et al 2001;Garber et al 2001;Haslinger et al 2004;Talantov et al 2005;Talbot et al 2005;Giordano et al 2006;Bonome et al 2008;Barretina et al 2010;Roessler et al 2010). However, TXNIP is overexpressed in some cancers suggesting that the role of TXNIP in tumor progression is likely to be context dependent (Talantov et al 2005;Sun et al 2006).…”