Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis

Jin Woo Kim, Qinghai Ye, Marshonna Forgues, Yidong Chen, Anuradha Budhu, Jessica Sime, Lorne J. Hofseth, Rashmi Kaul, Xin Wei Wang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P < .001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P < .001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention.

Original languageEnglish
Pages (from-to)518-527
Number of pages10
JournalHepatology
Volume39
Issue number2
DOIs
StatePublished - 1 Feb 2004

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Fibrosis
Hepatocellular Carcinoma
Genes
Neoplasms
Autoimmune Hepatitis
Alcoholic Liver Diseases
Hepatolenticular Degeneration
Hemochromatosis
Biliary Liver Cirrhosis
Neoplasm Genes
Chemoprevention
Virus Diseases
Oligonucleotide Array Sequence Analysis
Hepatitis B virus
Hepacivirus
Complementary DNA
Breast Neoplasms
Carcinoma
Lung
Messenger RNA

Cite this

Kim, J. W., Ye, Q., Forgues, M., Chen, Y., Budhu, A., Sime, J., ... Wang, X. W. (2004). Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis. Hepatology, 39(2), 518-527. https://doi.org/10.1002/hep.20053
Kim, Jin Woo ; Ye, Qinghai ; Forgues, Marshonna ; Chen, Yidong ; Budhu, Anuradha ; Sime, Jessica ; Hofseth, Lorne J. ; Kaul, Rashmi ; Wang, Xin Wei. / Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis. In: Hepatology. 2004 ; Vol. 39, No. 2. pp. 518-527.
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Kim, JW, Ye, Q, Forgues, M, Chen, Y, Budhu, A, Sime, J, Hofseth, LJ, Kaul, R & Wang, XW 2004, 'Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis', Hepatology, vol. 39, no. 2, pp. 518-527. https://doi.org/10.1002/hep.20053

Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis. / Kim, Jin Woo; Ye, Qinghai; Forgues, Marshonna; Chen, Yidong; Budhu, Anuradha; Sime, Jessica; Hofseth, Lorne J.; Kaul, Rashmi; Wang, Xin Wei.

In: Hepatology, Vol. 39, No. 2, 01.02.2004, p. 518-527.

Research output: Contribution to journalArticle

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AU - Kim, Jin Woo

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AU - Sime, Jessica

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Kim JW, Ye Q, Forgues M, Chen Y, Budhu A, Sime J et al. Cancer-Associated Molecular Signature in the Tissue Samples of Patients with Cirrhosis. Hepatology. 2004 Feb 1;39(2):518-527. https://doi.org/10.1002/hep.20053