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Sogbe M, Bilbao I, Marchese FP, Zazpe J, De Vito A, Pozuelo M, D’Avola D, Iñarrairaegui M, Berasain C, Arechederra M, Argemi J, Sangro B. Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment. Clin Mol Hepatol 2024; 30:177-190. [PMID: 38163441 PMCID: PMC11016491 DOI: 10.3350/cmh.2023.0426] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/14/2023] [Accepted: 12/27/2023] [Indexed: 01/03/2024] Open
Abstract
BACKGROUND/AIMS New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC. METHODS Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA. RESULTS Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09-28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis. CONCLUSION ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.
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Affiliation(s)
- Miguel Sogbe
- Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain
| | - Idoia Bilbao
- Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain
| | - Francesco P. Marchese
- University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Jon Zazpe
- University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Annarosaria De Vito
- University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Marta Pozuelo
- University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Delia D’Avola
- Clinica Universidad de Navarra, Internal Medicine Department, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
| | - Mercedes Iñarrairaegui
- Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
| | - Carmen Berasain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
- University of Navarra, Center for Applied Medical Research (CIMA), Hepatology Laboratory, Solid Tumors Program, Pamplona, Spain
| | - Maria Arechederra
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
- University of Navarra, Center for Applied Medical Research (CIMA), Hepatology Laboratory, Solid Tumors Program, Pamplona, Spain
| | - Josepmaria Argemi
- Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
- University of Navarra, Center for Applied Medical Research (CIMA), Hepatology Laboratory, Solid Tumors Program, Pamplona, Spain
| | - Bruno Sangro
- Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Clinica Universidad de Navarra, Liver Unit, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
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Norton PA, Mehta AS. Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review. World J Gastroenterol 2019; 25:2947-2960. [PMID: 31249452 PMCID: PMC6589740 DOI: 10.3748/wjg.v25.i23.2947] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 04/25/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.
AIM To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma
METHODS The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.
RESULTS A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.
CONCLUSION Amplification of genes involved in the de novo pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
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Affiliation(s)
- Pamela A Norton
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, United States
| | - Anand S Mehta
- Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425, United States
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Li SH, Li JP, Chen L, Liu JL. miR-146a induces apoptosis in neuroblastoma cells by targeting BCL11A. Med Hypotheses 2018; 117:21-27. [PMID: 30077189 DOI: 10.1016/j.mehy.2018.05.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/13/2018] [Accepted: 05/25/2018] [Indexed: 12/27/2022]
Abstract
Aberrant expression of miR-146a has been reported to be involved in the progression and metastasis of various types of human cancers; however, its potential role in human neuroblastoma is still poorly understood. The purpose of our study was to investigate the molecular mechanism and possible role of miR-146a in human neuroblastoma. In this study, targeted genes were predicted by bioinformatic analysis and confirmed by dual-Luciferase reporter assay. The expression level of miR-146a in the human neuroblastoma SK-N-SH cell line was detected by quantitative RT-PCR. We used flow cytometric analysis to determine apoptosis and necrosis of SK-N-SH cells after transfection with miR-146a inhibitor, miR-146a mimic, and negative controls. The expression level of target genes was detected by RT-PCR and Western blotting. We identified BCL11A as a target of miR-146a. Thus, miR-146a targets the 3'UTR of BCL11A and inhibits its mRNA and protein expression. Overexpression of miR-146a can inhibit the growth and promote the apoptosis of human neuroblastoma SK-N-SH cells through inhibiting the expression of BCL11A. Furthermore, we found that upregulation of BCL11A by miR-146a inhibitor can promote SK-N-SH cells growth and protect SK-N-SH cells against apoptosis. Our results showed that miR-146a is a potential tumor suppressor gene in human neuroblastoma via directly targeting BCL11A. These findings suggest that miR-146a might be a new candidate target for treatment of human neuroblastoma.
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Affiliation(s)
- Sheng-Hua Li
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Jin-Pin Li
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Lan Chen
- Department of Internal Medicine, The Second Affiliated Hospital of Guangxi Medical University in Nanning, China
| | - Jing-Li Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University in Nanning, China.
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Matboli M, Shafei AE, Shehata HH, Nabil N, Hossam N, Azazy AE, El-Tawdi AH, Abdel-Rahman O. Clinical significance of miRNA-autophagy transcript expression in patients with hepatocellular carcinoma. Biomark Med 2017; 11:641-656. [PMID: 28770611 DOI: 10.2217/bmm-2017-0049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
AIM This study integrates autophagy transcripts miRNAs expression based on bioinformatic analysis followed by clinical validation. METHODOLOGY Cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a level were investigated in the serum and tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C and healthy volunteers by quantitative real-time PCR. The prognostic power of this serum RNA panel was explored. RESULTS The expression of serum cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a were positive in 85.1, 94, 97.1 and 84.2% HCC patients, respectively and they were correlated with tissue levels. Our results suggested that the chosen panel is an independent prognostic factor for survival in patients with HCC. CONCLUSION The current work provides four RNA-based biomarker panel for HCC diagnosis and prognosis.
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Affiliation(s)
- Marwa Matboli
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Ayman E Shafei
- Biomedical Research Department, Military Armed Forces College of Medicine
| | - Hanan H Shehata
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Nesreen Nabil
- Department of Biochemistry, Faculty of pharmacy, Modern Univesity for Technology & Information, Cairo, Egypt
| | - Nourhan Hossam
- Oncology Diagnostic Unit, Medical Biochemistry & Molecular biology Department, Faculty of Medicine, Ain Shams University, PO box 11381, Abbassia, Cairo, Egypt
| | - Ahmed Em Azazy
- Undergraduate Student, Armed Forces College of Medicine, Cairo, Egypt
| | | | - Omar Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University
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Farid SG, Morris-Stiff G. "OMICS" technologies and their role in foregut primary malignancies. Curr Probl Surg 2015; 52:409-41. [PMID: 26527526 DOI: 10.1067/j.cpsurg.2015.08.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 08/03/2015] [Indexed: 12/18/2022]
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Zhang Z, Zhang Y, Sun XX, Ma X, Chen ZN. microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma. Mol Cancer 2015; 14:5. [PMID: 25608619 PMCID: PMC4326400 DOI: 10.1186/1476-4598-14-5] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 12/16/2014] [Indexed: 01/02/2023] Open
Abstract
Abstract Growing evidence indicates that miR-146a is involved in carcinogenesis and tumor progression in several human malignancies. However, the molecular details underlying miR-146a mediated regulation of its target genes and its precise biological function in cancer, especially in hepatocellular carcinoma (HCC) remains unclear. Methods The expression levels of genes including miR-146a, APC, VEGF and HAb18G were examined in HCC cell lines and patient specimens were compared with control levels using quantitative reverse transcription-PCR. The functions of miR-146a and HAb18G in migration/invasion and liver metastasis formation were determined by transwell and spleen injection assays, respectively. miR-146a related genes were determined by PCR array. The potential regulatory targets of miR-146a were determined by bioinformatics and prediction tools, correlation with target protein expression, and luciferase reporter assay. DNA methylation status of miR-146a promoter were performed by PCR analysis of bisulfite-modified genomic DNA. Results We demonstrated that miR-146a expression was markedly downregulated in hepatoma cells and hepatoma tissues compared to immortalized normal liver epithelial cells and normal hepatic tissues. DNA methylation of miR-146a promoter correlated with its downexpression and with liver cancer metastasis. The restoration of miR-146a dramatically suppressed HCC cell invasion and metastasis by repressing VEGF expression through upregulating APC, which inhibits β-catenin accumulation in nucleus, and downregulating NF-κB p65 by targeting HAb18G. In human HCC, miR-146a expression was negative correlated with increased HAb18G, VEGF, NF-κB p65 and beneficial prognosis. Conclusion This study identified a novel target of miR-146a and defined miR-146a as a crucial tumor suppressor in human HCC that acts through multiple pathways and mechanisms to suppress HCC invasion or metastasis. Electronic supplementary material The online version of this article (doi:10.1186/1476-4598-14-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | - Zhi-Nan Chen
- Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, P, R, China.
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Liu J, Ni W, Xiao M, Jiang F, Ni R. Decreased expression and prognostic role of mitogen-activated protein kinase phosphatase 4 in hepatocellular carcinoma. J Gastrointest Surg 2013; 17:756-765. [PMID: 23325341 DOI: 10.1007/s11605-013-2138-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 01/02/2013] [Indexed: 01/31/2023]
Abstract
PURPOSE This study aimed to investigate the potential role and prognostic significance of mitogen-activated protein kinase phosphatase 4 (MKP-4) in the pathology of hepatocellular carcinoma (HCC). METHODS Western blot analysis and quantitative real-time polymerase chain reaction were performed to detect MKP-4 expression in HCC tissues, pericarcinomatous liver (PCL) tissues, and proliferating HCC cells. The detailed role of MKP-4 was further explored by MKP-4 downregulation in HepG2 cells using small interfering RNA (siRNA). Specimens of 134 HCC patients who had undergone hepatic resection were immunohistochemically evaluated for MKP-4 expression. RESULTS MKP-4 protein and mRNA levels were significantly lower in HCC tissues than in PCL tissues. In vitro, its expression was gradually reduced following release of HepG2 cells from serum starvation. The cell counting kit-8 assay and Annexin-V-Fluos staining indicated that MKP-4 knockdown by siRNA in HCC cells enhanced cell survival and inhibited apoptosis. Univariate and multivariate analyses revealed that MKP-4 was a significant predictor for overall survival (OS) and time to recurrence (TTR). High MKP-4 expression was well correlated with prognosis independent of Edmondson grade and microvascular invasion (P < 0.001). CONCLUSIONS MKP-4 expression was downregulated in HCC tissues and proliferating HCC cells and correlated with OS and TTR, which suggested that MKP-4 is a candidate prognostic marker for HCC.
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Affiliation(s)
- Jinxia Liu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, China
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Sareeboot T, Punyarit P, Petmitr S. DNA amplification on chromosome 13q31.1 correlated with poor prognosis in colorectal cancer. Clin Exp Med 2010; 11:97-103. [DOI: 10.1007/s10238-010-0107-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2010] [Accepted: 07/26/2010] [Indexed: 01/04/2023]
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An Overview of Biomarkers and Molecular Signatures in HCC. Cancers (Basel) 2010; 2:809-23. [PMID: 24281095 PMCID: PMC3835106 DOI: 10.3390/cancers2020809] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2010] [Revised: 04/30/2010] [Accepted: 05/07/2010] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level is a useful marker for the detection and monitoring of HCC, AFP levels may remain normal in the patients even with advanced HCC. To identify useful biomarkers for HCC, many studies have been conducted on molecular events such as genetic and epigenetic alterations, and gene expression. This review summarizes recent studies of potential molecular markers for diagnosis and monitoring metastasis or recurrence of HCC.
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Song Z, Li R, You N, Tao K, Dou K. Loss of heterozygosity of the tumor suppressor gene Tg737 in the side population cells of hepatocellular carcinomas is associated with poor prognosis. Mol Biol Rep 2010; 37:4091-101. [PMID: 20300861 DOI: 10.1007/s11033-010-0069-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2009] [Accepted: 03/05/2010] [Indexed: 01/05/2023]
Abstract
Analysis of loss of heterozygosity (LOH) is a useful method for finding genetic alterations in tumor and precancerous lesion tissues. In this study, we analyzed LOH of the tumor suppressor gene Tg737 in side population cells of human hepatocellular carcinomas. Side population cells were sorted and identification by flow cytometry from suspensions of hepatocarcinoma or normal liver cells generated from 95 hepatocellular carcinoma and normal tissues, respectively. DNA was extracted from the two groups of side population cells and peripheral blood specimens. Five microsatellite markers on the Tg737 gene were used to analyze the frequency of loss of heterozygosity in the side population cells of the hepatocellular carcinoma. Twenty-four (25.30%) tumor samples had a large deletion in more than three microsatellite markers. The highest frequency of loss of heterozygosity was observed with the G64212 marker (78.75%) and the SHGC-57879 marker (75.95%). Statistical analysis of the correlation between loss of heterozygosity of Tg737 and clinicopathological features indicated a strong correlation between the two markers associated with the highest frequency of loss of heterozygosity and survival. The results indicate that loss of heterozygosity of the tumor suppressor gene Tg737 may play an important role in the carcinogenetic mechanism of liver cancer stem cells. In addition, the independent association between loss of heterozygosity at the SHGC-57879 and G64212 markers and worsened short-term survival in patients could be used as a novel prognostic predictor. Further studies of side population cells may contribute to the establishment of novel therapeutic strategies for hepatocellular carcinoma.
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Affiliation(s)
- Zhi Song
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, People's Republic of China
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Zhang SG, Song WQ, Gao YT, Yang B, Du Z. CD1d gene is a target for a novel amplicon at 1q22-23.1 in human hepatocellular carcinoma. Mol Biol Rep 2010; 37:381-387. [PMID: 19757161 DOI: 10.1007/s11033-009-9817-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2009] [Accepted: 09/03/2009] [Indexed: 01/05/2023]
Abstract
Genome copy number variation (CNV) is one of the mechanisms to regulate the expression level of genes which contributes to the development and progression of cancer. In order to investigate the regions of high-level amplification and potential target genes within these amplicons in hepatocellular carcinoma (HCC), we analyzed HCC cell line (TJ3ZX-01) for CNV regions at the whole genome level using GeneChip Human Mapping 500K array, and also examined the relative copy number and expression levels of the related genes at candidate amplicons in 41 HCC tissues via real-time fluorescence quantitative PCR methods. Through analysis of sequence tag site(STS) markers by quantitative PCR, The two candidate amplicons at 1q found by SNP array were shown to occur in56.1% (23/41) HCC samples at 1q21 and 80.5% (33/41) at 1q22-23.1. Wilcoxon signed rank test showed expression of CD1d, which located at amplicon of 1q22-23.1 increased significantly within tumor tissues compared with paired nontumor tissues. Our study provides evidences that a novel, high-level amplicon at 1q22-23.1 occurs in both HCC cell line and tissues. CD1d is a potential target for this amplicon in HCC. The up-regulation of CD1d may be used as a novel molecular signature for diagnosis and prognosis of HCC.
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Affiliation(s)
- Shi-Guang Zhang
- Laboratory of Chromosome Research, College of Life Science, Nankai University, Tianjin, China
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Pei Y, Zhang T, Renault V, Zhang X. An overview of hepatocellular carcinoma study by omics-based methods. Acta Biochim Biophys Sin (Shanghai) 2009; 41:1-15. [PMID: 19129945 DOI: 10.1093/abbs/gmn001] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most deadly malignancies worldwide. Scientists have been studying the molecular mechanism of HCC for years, but the understanding of it remains incomplete and scattered across the literature at different molecular levels. Chromosomal aberrations, epigenetic abnormality and changes of gene expression have been reported in HCC. High-throughput omics technologies have been widely applied, aiming at the discovery of candidate biomarkers for cancer staging, prediction of recurrence and prognosis, and treatment selection. Large amounts of data on genetic and epigenetic abnormalities, gene expression profiles, microRNA expression profiles and proteomics have been accumulating, and bioinformatics is playing a more and more important role. In this paper, we review the current omics-based studies on HCC at the levels of genomics, transcriptomics and proteomics. Integrating observations from multiple aspects is an essential step toward the systematic understanding of the disease.
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Affiliation(s)
- Yunfei Pei
- TNLIST/Department of Automation, Bioinformatics and Bioinformatics Division, MOE Key Laboratory, Tsinghua University, Beijing, China
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