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Article: MicroRNA expression, survival, and response to interferon in liver cancer
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TitleMicroRNA expression, survival, and response to interferon in liver cancer
 
AuthorsJi, J2
Shi, J2 4
Budhu, A2
Yu, Z2
Forgues, M2
Roessler, S2
Ambs, S2
Chen, Y2
Meltzer, PS2
Croce, CM3
Qin, LX4
Man, K1
Lo, CM1
Lee, J1
Ng, IOL1
Fan, J4
Tang, ZY4
Sun, HC4
Wang, XW2
 
Issue Date2009
 
PublisherMassachusetts Medical Society. The Journal's web site is located at http://content.nejm.org/
 
CitationNew England Journal Of Medicine, 2009, v. 361 n. 15, p. 1437-1447 [How to Cite?]
DOI: http://dx.doi.org/10.1056/NEJMoa0901282
 
AbstractBACKGROUND: Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. METHODS: We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase-polymerase- chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. RESULTS: In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor κB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. CONCLUSIONS: The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa. Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 
ISSN0028-4793
2013 Impact Factor: 54.420
 
DOIhttp://dx.doi.org/10.1056/NEJMoa0901282
 
PubMed Central IDPMC2786938
 
ISI Accession Number IDWOS:000270540000005
Funding AgencyGrant Number
Intramural Research Program of the Center for Cancer Research of the National Cancer InstituteZ01-BC 010313
Z01-BC 010876
Funding Information:

Supported in part by grants (Z01-BC 010313 and Z01-BC 010876) from the Intramural Research Program of the Center for Cancer Research of the National Cancer Institute.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorJi, J
 
dc.contributor.authorShi, J
 
dc.contributor.authorBudhu, A
 
dc.contributor.authorYu, Z
 
dc.contributor.authorForgues, M
 
dc.contributor.authorRoessler, S
 
dc.contributor.authorAmbs, S
 
dc.contributor.authorChen, Y
 
dc.contributor.authorMeltzer, PS
 
dc.contributor.authorCroce, CM
 
dc.contributor.authorQin, LX
 
dc.contributor.authorMan, K
 
dc.contributor.authorLo, CM
 
dc.contributor.authorLee, J
 
dc.contributor.authorNg, IOL
 
dc.contributor.authorFan, J
 
dc.contributor.authorTang, ZY
 
dc.contributor.authorSun, HC
 
dc.contributor.authorWang, XW
 
dc.date.accessioned2010-09-06T09:42:11Z
 
dc.date.available2010-09-06T09:42:11Z
 
dc.date.issued2009
 
dc.description.abstractBACKGROUND: Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. METHODS: We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase-polymerase- chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. RESULTS: In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor κB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. CONCLUSIONS: The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa. Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationNew England Journal Of Medicine, 2009, v. 361 n. 15, p. 1437-1447 [How to Cite?]
DOI: http://dx.doi.org/10.1056/NEJMoa0901282
 
dc.identifier.citeulike5955877
 
dc.identifier.doihttp://dx.doi.org/10.1056/NEJMoa0901282
 
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dc.identifier.hkuros168549
 
dc.identifier.isiWOS:000270540000005
Funding AgencyGrant Number
Intramural Research Program of the Center for Cancer Research of the National Cancer InstituteZ01-BC 010313
Z01-BC 010876
Funding Information:

Supported in part by grants (Z01-BC 010313 and Z01-BC 010876) from the Intramural Research Program of the Center for Cancer Research of the National Cancer Institute.

 
dc.identifier.issn0028-4793
2013 Impact Factor: 54.420
 
dc.identifier.issue15
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2786938
 
dc.identifier.pmid19812400
 
dc.identifier.scopuseid_2-s2.0-70349871321
 
dc.identifier.spage1437
 
dc.identifier.urihttp://hdl.handle.net/10722/88347
 
dc.identifier.volume361
 
dc.languageeng
 
dc.publisherMassachusetts Medical Society. The Journal's web site is located at http://content.nejm.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNew England Journal of Medicine
 
dc.relation.referencesReferences in Scopus
 
dc.rightsNew England Journal of Medicine. Copyright © Massachusetts Medical Society.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshAntiviral Agents - therapeutic use
 
dc.subject.meshCarcinoma, Hepatocellular - drug therapy - genetics - mortality
 
dc.subject.meshGene Expression
 
dc.subject.meshInterferon-alpha - therapeutic use
 
dc.subject.meshLiver Neoplasms - drug therapy - genetics - mortality
 
dc.titleMicroRNA expression, survival, and response to interferon in liver cancer
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. National Cancer Institute
  3. Ohio State University Comprehensive Cancer Center
  4. Fudan University