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Article: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma
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TitleMicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma
 
AuthorsSchetter, AJ1 1
Leung, SY2
Sohn, JJ1
Zanetti, KA1 1
Bowman, ED1
Yanaihara, N1
Yuen, ST2
Chan, TL2
Kwong, DLW2
Au, GKH2
Liu, CG
Calin, GA3
Croce, CM
Harris, CC1 1
 
Issue Date2008
 
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
 
CitationJama - Journal Of The American Medical Association, 2008, v. 299 n. 4, p. 425-436 [How to Cite?]
DOI: http://dx.doi.org/10.1001/jama.299.4.425
 
AbstractContext: MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome. Objective: To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome. Design, Setting, and Patients: MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort. Main Outcome Measures: MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. Results: Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P<.001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P<.001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome. Conclusions: Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome. ©2008 American Medical Association. All rights reserved.
 
ISSN0098-7484
2012 Impact Factor: 29.978
2012 SCImago Journal Rankings: 4.843
 
DOIhttp://dx.doi.org/10.1001/jama.299.4.425
 
ISI Accession Number IDWOS:000252724500020
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSchetter, AJ
 
dc.contributor.authorLeung, SY
 
dc.contributor.authorSohn, JJ
 
dc.contributor.authorZanetti, KA
 
dc.contributor.authorBowman, ED
 
dc.contributor.authorYanaihara, N
 
dc.contributor.authorYuen, ST
 
dc.contributor.authorChan, TL
 
dc.contributor.authorKwong, DLW
 
dc.contributor.authorAu, GKH
 
dc.contributor.authorLiu, CG
 
dc.contributor.authorCalin, GA
 
dc.contributor.authorCroce, CM
 
dc.contributor.authorHarris, CC
 
dc.date.accessioned2010-05-31T03:33:20Z
 
dc.date.available2010-05-31T03:33:20Z
 
dc.date.issued2008
 
dc.description.abstractContext: MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome. Objective: To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome. Design, Setting, and Patients: MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort. Main Outcome Measures: MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. Results: Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P<.001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P<.001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome. Conclusions: Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome. ©2008 American Medical Association. All rights reserved.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJama - Journal Of The American Medical Association, 2008, v. 299 n. 4, p. 425-436 [How to Cite?]
DOI: http://dx.doi.org/10.1001/jama.299.4.425
 
dc.identifier.citeulike2506996
 
dc.identifier.doihttp://dx.doi.org/10.1001/jama.299.4.425
 
dc.identifier.epage436
 
dc.identifier.hkuros166349
 
dc.identifier.hkuros143519
 
dc.identifier.isiWOS:000252724500020
 
dc.identifier.issn0098-7484
2012 Impact Factor: 29.978
2012 SCImago Journal Rankings: 4.843
 
dc.identifier.issue4
 
dc.identifier.pmid18230780
 
dc.identifier.scopuseid_2-s2.0-38749089854
 
dc.identifier.spage425
 
dc.identifier.urihttp://hdl.handle.net/10722/58604
 
dc.identifier.volume299
 
dc.languageeng
 
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJAMA - Journal of the American Medical Association
 
dc.relation.referencesReferences in Scopus
 
dc.titleMicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma
 
dc.typeArticle
 
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<contributor.author>Bowman, ED</contributor.author>
<contributor.author>Yanaihara, N</contributor.author>
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Author Affiliations
  1. National Cancer Institute
  2. The University of Hong Kong
  3. University of Texas M. D. Anderson Cancer Center