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Unique MicroRNA Expression Signature Predicts Survival, Metastases and Recurrence of HCC

ABSTRACT: In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence. Keywords: disease state design

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE6857 | GEO | 2008/01/14

SECONDARY ACCESSION(S): PRJNA99101

REPOSITORIES: GEO

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Unique MicroRNA Expression Signature Predicts Survival, Metastases and Recurrence of HCC

Project description:In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence. Keywords: disease state design Gene expression profiles were conducted in primary HCC and corresponding noncancerous hepatic tissues from 244 Chinese HCC patients. A total of 134 well-defined cases were used as a training group. Among them, 30 had primary HCC lesions accompanied by tumor emboli and 104 had solitary HCC with no metastasis/recurrence found at follow-up (3 yr). We used a testing group of 110 independent cases. The testing cases included 43 multinodular and 67 solitary HCC. In addition, eight normal liver tissues from disease-free patients were included as normal controls. In the analysis of the 244 HCC cases, RNA was isolated in a pairwise fashion from tumor or non-tumor tissue and samples were selected in random order for miRNA analysis to avoid grouping bias.

2008-01-14 | E-GEOD-6857 | biostudies-arrayexpress

TERT Promoter Mutations Combined with TP53 Mutations as Potential Biomarkers for Hepatocellular Carcinoma Recurrence and Prognosis

Project description:Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and ranks among the most lethal malignancies globally, primarily due to its high rates of recurrence and metastasis. Despite the urgency, no reliable biomarkers currently exist for predicting tumor recurrence in HCC. Telomerase reverse transcriptase (TERT) promoter mutations (TERTpm) and cellular tumor antigen p53 mutations (TP53m) have been frequently documented in HCC, but their combined clinical significance remains undefined. In this study, we investigated the clinical implications of TERTpm, TP53m, and their co-occurrence in 50 HCC tissue samples using the next-generation sequencing (NGS) technology. We identified TERTpm (C228T) and TP53m in 16 (32%) and 24 (48%) samples, respectively. Our findings indicate that these mutations are more prevalent in male patients (100% for TERTpm, 83.33% for TP53m), in those with solitary tumors (87.5% for both), in individuals with G2-G3 hepatitis (100% / 83.3%), and in cases of moderately differentiated tumors (75.0% / 83.3%). Furthermore, patients with both TERTpm and TP53m exhibited a significantly higher risk of tumor relapse (P<0.05) and shorter progression-free survival (P<0.05). Collectively, our results suggest that presence of both TERTpm and TP53m may serve as a robust predictor of tumor recurrence and a marker of poor prognosis in HCC.

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Project description:Recurrence and metastasis remain the major obstacles to prognosis of hepatocellular carcinoma (HCC), but the relationship between proteomics and poor prognosis need to be studied more systematically. In this study, we performed the proteomics data collected from 85 HCC tumors and 18 adjacent normal tissues (ANTs) to establish the proteomics profiles of HCC and reveal the correlation between poteomics and ubiquitomics features of tumor tissues in HCC. Our data bring new insights on multi-omics data and have the potential to further understand the relationship between post-translational modification (PTM) levels of proteins and different molecular and clinical features of HCC patients. XAD1—XAD18 --- HCC adjacent normal tissues XC1—XC85--- HCC tumor tissues

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Affymetrix SNP array data for hepatocellular carcinoma tissue

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Gene Expression Profiles of both tumor and adjacent non-tumor liver Identify Hepatocellular Carcinoma Patients at High Risk of Recurrence after Curative Hepatectomy

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Identification of differentially expressed microRNAs between human HCC tumors with and without vascular invasion [batch 2]

Project description:Non-coding microRNAs (miRNAs) mainly regulate the expression of targeted genes by regulating mRNA degradation or repressing their protein translation. Recent research has shown miRNAs to have remarkable potential as biomarkers for the diagnosis and prognosis of disease. Since vascular invasion (VI) provides a direct path for solid tumor metastasis/recurrence, in this study we investigated if miRNAs can serve as a biomarker to differentiate between VI- and VI+ tumors. MiRNA microarray profiling was then performed on 172 human HCC tumors samples with or without VI from HCC patients.

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Identification of differentially expressed microRNAs between human HCC tumors with and without vascular invasion [batch 1]

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Gene Expression Profiles of both tumor and adjacent non-tumor liver Identify Hepatocellular Carcinoma Patients at High Risk of Recurrence after Curative Hepatectomy

Project description:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. It is crucial to identify patients with a high risk of recurrence and develop more intensified or targeted treatment strategy to improve disease outcome. In the training set, tumor and non-tumor liver were profiled separately, and each was used to generate a prediction model which was validated with the use of independent validation set.

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Project description:Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. The poor prognosis of HCC is mostly due to recurrence and tumor metastasis. In order to better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by using quantitative proteomics and bioinformatics analysis. As a result, we identified 331 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that metabolism and cytoskeleton biological progresses are greatly involved with HCC metastasis. Furthermore, integrative network analysis revealed a rich-club organization in the PPI network indicating a hub center of connections, including several well-known cancer related proteins, such as SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and pyruvate kinase M2 (PKM2). Moreover, the differential expressions of two identified proteins, including PKM2 and actin-related protein 2/3 complex subunit 4 (ARPC4), were validated using Western blotting. These two proteins were identified as potential prognostic markers for HCC by using survival rate analysis.

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