Future of molecular profiling of human hepatocellular carcinoma

National Cancer Institute, Laboratory of Human Carcinogenesis, Center for Cancer Research, NIH, 37 Convent Drive, Bldg. 37, Rm. 3044A, Bethesda, MD 20892-4258, USA.
Future Oncology (Impact Factor: 2.61). 09/2007; 3(4):429-39. DOI: 10.2217/14796694.3.4.429
Source: PubMed

ABSTRACT Hepatocellular carcinoma (HCC) is a fatal disease occurring worldwide and developing mainly in chronic liver diseased patients. Despite routine screening of individuals at high risk, most of the patients are diagnosed at late stages of HCC. In addition, the recurrence rate after surgical resection of small tumors is high. Molecular profiling, including expression analysis, comparative genomics and proteomics, provides powerful tools to gain insight into the molecular mechanisms underlying carcinogenesis. Advances in bioinformatics have also allowed for the evaluation of large data sets. Therefore, molecular profiling of HCC using a Biological Expression Network Discovery (BLEND) strategy that integrates global molecular profiling data, including mRNA, miRNA, DNA methylation and DNA copy numbers from both the tumor and the surrounding microenvironment, along with mechanistic studies, may improve the diagnosis, treatment and prognosis of HCC patients. Such an approach will provide mechanistic insight into the pathogenesis of HCC, potentially leading to personalized medicine and the identification of new therapeutic targets.

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    • "Recently, microRNAs (miRNAs), small noncoding RNAs of ∼22 nucleotides (nt) in length, have been implicated in several carcinogenic processes by acting either as tumor suppressors or oncogenes. Studies have shown that miRNAs expression profiles can classify human cancers [1] [2] [3] [4] [5] [6] [7]. Furthermore , some reports also suggest that cell-free circulating miRNAs existed in serum and plasma [8] [9] [10] [11] [12] [13] [14]. "
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    ABSTRACT: It is reported that different microRNA (miRNA) profiles can be detected in the blood of cancer patients. We investigated that whether the key serum miRNAs could discriminate patients with and without breast cancer. This study was divided into three parts: (1) miRNA marker discovery using SOLiD sequencing-based miRNA profiling on cancerous and adjacent noncancerous breast tissue of one breast cancer patient; (2) marker selection and validation by real-time PCR on a small set of serum; (3) gene ontology analysis of the key miRNA target genes. Of genome-wide tissue miRNA expression analysis, five miRNAs were found to be altered more than fivefold by SOLiD sequencing (i.e., miR-29a, miR-23a, miR-23b, miR-192, and miR-21). All the five miRNAs were validated on the 20 breast cancer patients and 20 controls. miR-29a and miR-21 were significantly increased in the serum of breast cancer patients (P < .05). Gene ontology analysis of the target genes revealed enrichment for special biological process categories, that is, signal transduction, development, apoptosis, cell proliferation, and cell adhesion. SOLiD sequencing provides a promising method for cancer-related miRNA profiling. Serum miRNAs may be useful biomarkers for breast cancer detection.
    BioMed Research International 05/2011; 2011(1110-7243):597145. DOI:10.1155/2011/597145 · 2.71 Impact Factor
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    • "While over 80% of HCC occurs in the background of inflammation, mainly caused by viral hepatitis [1] only a fraction of patients with CLD develop HCC, suggesting that the individual genetic background contributes to HCC risk. Patients with HCC currently have a very poor outcome, partly due to the advanced stages of disease at clinical presentation and to its heterogeneity. "
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    ABSTRACT: To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1962 individuals with HCC, 1430 control subjects, and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B-, or PGD-related pathways might be involved in the pathogenesis of this malignancy.
    Journal of Hepatology 12/2010; 54(4):823-4. DOI:10.1016/j.jhep.2010.10.035 · 10.40 Impact Factor
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    ABSTRACT: Small RNA molecules such as microRNAs, for many years considered to be superfluous genomic material, are now known to play important regulatory roles in apoptosis, cell proliferation and differentiation, angiogenesis and thus in carcinogenesis. Primary liver carcinomas such as hepatocellular carcinomas, cholangiocarcinomas and mixed variants show a rising incidence with high mortality among affected patients but lack effective targeted therapies except the new multiple kinase inhibitor Sorafenib. This review elucidates the recent contributions of miRNA gene expression analyses to a better understanding of the complex molecular interactions in liver carcinogenesis and highlights their future promise to provide novel tools for improved diagnostics, more accurate prognostic assessment and tailored molecular therapies in liver cancer.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 04/2008; 7(2):104-13. · 2.19 Impact Factor
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