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Article: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma

TitleMicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma
Authors
Issue Date2008
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
Citation
JAMA - Journal Of The American Medical Association, 2008, v. 299 n. 4, p. 425-436 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/58604
ISSN
2014 Impact Factor: 35.289
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSchetter, AJen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorSohn, JJen_HK
dc.contributor.authorZanetti, KAen_HK
dc.contributor.authorBowman, EDen_HK
dc.contributor.authorYanaihara, Nen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorKwong, DLWen_HK
dc.contributor.authorAu, GKHen_HK
dc.contributor.authorLiu, CGen_HK
dc.contributor.authorCalin, GAen_HK
dc.contributor.authorCroce, CMen_HK
dc.contributor.authorHarris, CCen_HK
dc.date.accessioned2010-05-31T03:33:20Z-
dc.date.available2010-05-31T03:33:20Z-
dc.date.issued2008en_HK
dc.identifier.citationJAMA - Journal Of The American Medical Association, 2008, v. 299 n. 4, p. 425-436en_HK
dc.identifier.issn0098-7484en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58604-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtlen_HK
dc.relation.ispartofJAMA - Journal of the American Medical Associationen_HK
dc.titleMicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_HK
dc.identifier.emailChan, TL:tlchan@hku.hken_HK
dc.identifier.emailKwong, DLW:dlwkwong@hku.hken_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityKwong, DLW=rp00414en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1001/jama.299.4.425en_HK
dc.identifier.pmid18230780-
dc.identifier.pmcidPMC2614237-
dc.identifier.scopuseid_2-s2.0-38749089854en_HK
dc.identifier.hkuros166349en_HK
dc.identifier.hkuros143519en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-38749089854&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume299en_HK
dc.identifier.issue4en_HK
dc.identifier.spage425en_HK
dc.identifier.epage436en_HK
dc.identifier.isiWOS:000252724500020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSchetter, AJ=6506741091en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridSohn, JJ=23482576300en_HK
dc.identifier.scopusauthoridZanetti, KA=14062743900en_HK
dc.identifier.scopusauthoridBowman, ED=7102143007en_HK
dc.identifier.scopusauthoridYanaihara, N=8696702400en_HK
dc.identifier.scopusauthoridYuen, ST=8323342200en_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridKwong, DLW=15744231600en_HK
dc.identifier.scopusauthoridAu, GKH=7003748615en_HK
dc.identifier.scopusauthoridLiu, CG=26643345100en_HK
dc.identifier.scopusauthoridCalin, GA=7004623029en_HK
dc.identifier.scopusauthoridCroce, CM=7202975031en_HK
dc.identifier.scopusauthoridHarris, CC=7403874710en_HK
dc.identifier.citeulike2506996-

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