Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma

Elisa Wurmbach, Ying Bei Chen, Greg Khitrov, Weijia Zhang, Sasan Roayaie, Myron Schwartz, Isabel Fiel, Swan Thung, Vincenzo Mazzaferro, Jordi Bruix, Erwin Bottinger, Scott Friedman, Samuel Waxman, Josep M. Llovet

Research output: Contribution to journalArticle

386 Citations (Scopus)

Abstract

Although HCC is the third-leading cause of cancer-related deaths worldwide, there is only an elemental understanding of its molecular pathogenesis. In western countries, HCV infection is the main etiology underlying this cancer's accelerating incidence. To characterize the molecular events of the hepatocarcinogenic process, and to identify new biomarkers for early HCC, the gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC, including 4 neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. We identified gene signatures that accurately reflect the pathological progression of disease at each stage. Eight genes distinguish between control and cirrhosis, 24 between cirrhosis and dysplasia, 93 between dysplasia and early HCC, and 9 between early and advanced HCC. Using quantitative real-time reverse-transcription PCR, we validated several novel molecular tissue markers for early HCC diagnosis, specifically induction of abnormal spindle-like, microcephaly-associated protein, hyaluronan-mediated motility receptor, primase 1, erythropoietin, and neuregulin 1. In addition, pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then upregulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages. Conclusion: These findings provide a comprehensive molecular portrait of genomic changes in progressive HCV-related HCC.

Original languageEnglish
Pages (from-to)938-947
Number of pages10
JournalHepatology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Hepatocellular Carcinoma
Fibrosis
Genome
DNA Primase
Neuregulin-1
Genes
Neoplasms
Microcephaly
Toll-Like Receptors
Erythropoietin
Infection
DNA Replication
Transcriptome
DNA Repair
Reverse Transcription
Disease Progression
Early Diagnosis
Cell Cycle
Carcinogenesis
Up-Regulation

ASJC Scopus subject areas

  • Hepatology

Cite this

Wurmbach, E., Chen, Y. B., Khitrov, G., Zhang, W., Roayaie, S., Schwartz, M., ... Llovet, J. M. (2007). Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology, 45(4), 938-947. https://doi.org/10.1002/hep.21622

Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. / Wurmbach, Elisa; Chen, Ying Bei; Khitrov, Greg; Zhang, Weijia; Roayaie, Sasan; Schwartz, Myron; Fiel, Isabel; Thung, Swan; Mazzaferro, Vincenzo; Bruix, Jordi; Bottinger, Erwin; Friedman, Scott; Waxman, Samuel; Llovet, Josep M.

In: Hepatology, Vol. 45, No. 4, 04.2007, p. 938-947.

Research output: Contribution to journalArticle

Wurmbach, E, Chen, YB, Khitrov, G, Zhang, W, Roayaie, S, Schwartz, M, Fiel, I, Thung, S, Mazzaferro, V, Bruix, J, Bottinger, E, Friedman, S, Waxman, S & Llovet, JM 2007, 'Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma', Hepatology, vol. 45, no. 4, pp. 938-947. https://doi.org/10.1002/hep.21622
Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, Schwartz M et al. Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 2007 Apr;45(4):938-947. https://doi.org/10.1002/hep.21622
Wurmbach, Elisa ; Chen, Ying Bei ; Khitrov, Greg ; Zhang, Weijia ; Roayaie, Sasan ; Schwartz, Myron ; Fiel, Isabel ; Thung, Swan ; Mazzaferro, Vincenzo ; Bruix, Jordi ; Bottinger, Erwin ; Friedman, Scott ; Waxman, Samuel ; Llovet, Josep M. / Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. In: Hepatology. 2007 ; Vol. 45, No. 4. pp. 938-947.
@article{c354516d73134de1bc412ac880c83032,
title = "Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma",
abstract = "Although HCC is the third-leading cause of cancer-related deaths worldwide, there is only an elemental understanding of its molecular pathogenesis. In western countries, HCV infection is the main etiology underlying this cancer's accelerating incidence. To characterize the molecular events of the hepatocarcinogenic process, and to identify new biomarkers for early HCC, the gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC, including 4 neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. We identified gene signatures that accurately reflect the pathological progression of disease at each stage. Eight genes distinguish between control and cirrhosis, 24 between cirrhosis and dysplasia, 93 between dysplasia and early HCC, and 9 between early and advanced HCC. Using quantitative real-time reverse-transcription PCR, we validated several novel molecular tissue markers for early HCC diagnosis, specifically induction of abnormal spindle-like, microcephaly-associated protein, hyaluronan-mediated motility receptor, primase 1, erythropoietin, and neuregulin 1. In addition, pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then upregulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages. Conclusion: These findings provide a comprehensive molecular portrait of genomic changes in progressive HCV-related HCC.",
author = "Elisa Wurmbach and Chen, {Ying Bei} and Greg Khitrov and Weijia Zhang and Sasan Roayaie and Myron Schwartz and Isabel Fiel and Swan Thung and Vincenzo Mazzaferro and Jordi Bruix and Erwin Bottinger and Scott Friedman and Samuel Waxman and Llovet, {Josep M.}",
year = "2007",
month = "4",
doi = "10.1002/hep.21622",
language = "English",
volume = "45",
pages = "938--947",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma

AU - Wurmbach, Elisa

AU - Chen, Ying Bei

AU - Khitrov, Greg

AU - Zhang, Weijia

AU - Roayaie, Sasan

AU - Schwartz, Myron

AU - Fiel, Isabel

AU - Thung, Swan

AU - Mazzaferro, Vincenzo

AU - Bruix, Jordi

AU - Bottinger, Erwin

AU - Friedman, Scott

AU - Waxman, Samuel

AU - Llovet, Josep M.

PY - 2007/4

Y1 - 2007/4

N2 - Although HCC is the third-leading cause of cancer-related deaths worldwide, there is only an elemental understanding of its molecular pathogenesis. In western countries, HCV infection is the main etiology underlying this cancer's accelerating incidence. To characterize the molecular events of the hepatocarcinogenic process, and to identify new biomarkers for early HCC, the gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC, including 4 neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. We identified gene signatures that accurately reflect the pathological progression of disease at each stage. Eight genes distinguish between control and cirrhosis, 24 between cirrhosis and dysplasia, 93 between dysplasia and early HCC, and 9 between early and advanced HCC. Using quantitative real-time reverse-transcription PCR, we validated several novel molecular tissue markers for early HCC diagnosis, specifically induction of abnormal spindle-like, microcephaly-associated protein, hyaluronan-mediated motility receptor, primase 1, erythropoietin, and neuregulin 1. In addition, pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then upregulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages. Conclusion: These findings provide a comprehensive molecular portrait of genomic changes in progressive HCV-related HCC.

AB - Although HCC is the third-leading cause of cancer-related deaths worldwide, there is only an elemental understanding of its molecular pathogenesis. In western countries, HCV infection is the main etiology underlying this cancer's accelerating incidence. To characterize the molecular events of the hepatocarcinogenic process, and to identify new biomarkers for early HCC, the gene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC, including 4 neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. We identified gene signatures that accurately reflect the pathological progression of disease at each stage. Eight genes distinguish between control and cirrhosis, 24 between cirrhosis and dysplasia, 93 between dysplasia and early HCC, and 9 between early and advanced HCC. Using quantitative real-time reverse-transcription PCR, we validated several novel molecular tissue markers for early HCC diagnosis, specifically induction of abnormal spindle-like, microcephaly-associated protein, hyaluronan-mediated motility receptor, primase 1, erythropoietin, and neuregulin 1. In addition, pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then upregulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages. Conclusion: These findings provide a comprehensive molecular portrait of genomic changes in progressive HCV-related HCC.

UR - http://www.scopus.com/inward/record.url?scp=34247549347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247549347&partnerID=8YFLogxK

U2 - 10.1002/hep.21622

DO - 10.1002/hep.21622

M3 - Article

C2 - 17393520

AN - SCOPUS:34247549347

VL - 45

SP - 938

EP - 947

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -