You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


ABOUT JAMA
Advanced Search

Welcome   | My Account | E-mail Alerts | Access Rights | Sign In


  Vol. 299 No. 4, January 30, 2008 TABLE OF CONTENTS
  JAMA
  •  Online Features
  Preliminary Communication
 This Article
 •Full text
 •PDF
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on HighWire
 •Citing articles on Web of Science (89)
 •Contact me when this article is cited
 Related Content
 •Related letter
 •Similar articles in JAMA
 Topic Collections
 •Oncology
 •Colon Cancer
 •Oncology, Other
 •Prognosis/ Outcomes
 •Genetics, Other
 •Alert me on articles by topic
 Social Bookmarking
  Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit Add to Technorati Add to Twitter What's this?

MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma

Aaron J. Schetter, PhD, MPH; Suet Yi Leung, MD; Jane J. Sohn, PhD; Krista A. Zanetti, PhD, MPH; Elise D. Bowman, MS; Nozomu Yanaihara, MD, PhD; Siu Tsan Yuen, MD; Tsun Leung Chan, MD; Dora L. W. Kwong, MD; Gordon K. H. Au, MD; Chang-Gong Liu, PhD; George A. Calin, MD, PhD; Carlo M. Croce, MD; Curtis C. Harris, MD

JAMA. 2008;299(4):425-436.

Context  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, 2004, 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.


Author Affiliations: Laboratory of Human Carcinogenesis, Center for Cancer Research (Drs Schetter, Sohn, Zanetti, Yanaihara, and Harris and Ms Bowman) and Cancer Prevention Fellowship Program, Office of Preventive Oncology (Drs Schetter and Zanetti), National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Departments of Pathology (Drs Leung, Yuen, and Chan) and Clinical Oncology (Drs Kwong and Au), University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong; Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Comprehensive Cancer Center, Columbus, Ohio (Drs Liu and Croce); and Department of Experimental Therapeutics, M. D. Anderson Cancer Center, Houston, Texas (Dr Calin).



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter     What's this?

RELATED LETTER

MicroRNA Expression in Colon Adenocarcinoma
and
JAMA. ;299():2628-2628.
FULL TEXT  


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

MicroRNAs: tools for cancer diagnostics
Paranjape et al.
Gut 2009;58:1546-1554.
ABSTRACT | FULL TEXT  

Distinct MicroRNA Alterations Characterize High- and Low-Grade Bladder Cancer
Catto et al.
Cancer Res. 2009;69:8472-8481.
ABSTRACT | FULL TEXT  

microRNA-21 Negatively Regulates Cdc25A and Cell Cycle Progression in Colon Cancer Cells
Wang et al.
Cancer Res. 2009;69:8157-8165.
ABSTRACT | FULL TEXT  

MicroRNA Expression, Survival, and Response to Interferon in Liver Cancer
Ji et al.
NEJM 2009;361:1437-1447.
ABSTRACT | FULL TEXT  

Plasma microRNAs: a potential biomarker for colorectal cancer?
Schetter and Harris
Gut 2009;58:1318-1319.
FULL TEXT  

Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening
Ng et al.
Gut 2009;58:1375-1381.
ABSTRACT | FULL TEXT  

MicroRNA Expression in Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus: Associations with Survival
Mathe et al.
Clin. Cancer Res. 2009;15:6192-6200.
ABSTRACT | FULL TEXT  

Association of Inflammation-Related and microRNA Gene Expression with Cancer-Specific Mortality of Colon Adenocarcinoma
Schetter et al.
Clin. Cancer Res. 2009;15:5878-5887.
ABSTRACT | FULL TEXT  

MicroRNA Expression Signatures in Barrett's Esophagus and Esophageal Adenocarcinoma
Yang et al.
Clin. Cancer Res. 2009;15:5744-5752.
ABSTRACT | FULL TEXT  

ST14 (Suppression of Tumorigenicity 14) Gene Is a Target for miR-27b, and the Inhibitory Effect of ST14 on Cell Growth Is Independent of miR-27b Regulation
Wang et al.
J. Biol. Chem. 2009;284:23094-23106.
ABSTRACT | FULL TEXT  

MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers
Seike et al.
Proc. Natl. Acad. Sci. USA 2009;106:12085-12090.
ABSTRACT | FULL TEXT  

MicroRNA Classifiers for Predicting Prognosis of Squamous Cell Lung Cancer
Raponi et al.
Cancer Res. 2009;69:5776-5783.
ABSTRACT | FULL TEXT  

Pathogenetic and Clinical Relevance of MicroRNAs in Colorectal Cancer
VALERI et al.
Cancer Genomics Proteomics 2009;6:195-204.
ABSTRACT | FULL TEXT  

MiR-21 Indicates Poor Prognosis in Tongue Squamous Cell Carcinomas as an Apoptosis Inhibitor
Li et al.
Clin. Cancer Res. 2009;15:3998-4008.
ABSTRACT | FULL TEXT  

Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development
Yamamichi et al.
Clin. Cancer Res. 2009;15:4009-4016.
ABSTRACT | FULL TEXT  

Combination of Microsatellite Instability and Lymphocytic Infiltrate as a Prognostic Indicator in Colon Cancer
Chang et al.
Arch Surg 2009;144:511-515.
ABSTRACT | FULL TEXT  

Epigenetic Silencing of the Tumor Suppressor MicroRNA Hsa-miR-124a Regulates CDK6 Expression and Confers a Poor Prognosis in Acute Lymphoblastic Leukemia
Agirre et al.
Cancer Res. 2009;69:4443-4453.
ABSTRACT | FULL TEXT  

MiR-sensing chemotherapy resistance in CLL
Calin
Blood 2009;113:3652-3653.
FULL TEXT  

MiRNAs and Cancer
Visone and Croce
Am. J. Pathol. 2009;174:1131-1138.
ABSTRACT | FULL TEXT  

microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells
Bandres et al.
Clin. Cancer Res. 2009;15:2281-2290.
ABSTRACT | FULL TEXT  

MicroRNA-21 Regulates the Proliferation and Invasion in Esophageal Squamous Cell Carcinoma
Hiyoshi et al.
Clin. Cancer Res. 2009;15:1915-1922.
ABSTRACT | FULL TEXT  

Epigenetic Regulation of MicroRNAs in Acute Lymphoblastic Leukemia
Roman-Gomez et al.
JCO 2009;27:1316-1322.
ABSTRACT | FULL TEXT  

Reciprocal Regulation of Myocardial microRNAs and Messenger RNA in Human Cardiomyopathy and Reversal of the microRNA Signature by Biomechanical Support
Matkovich et al.
Circulation 2009;119:1263-1271.
ABSTRACT | FULL TEXT  

Coordinated Regulation of Cell Cycle Transcripts by p53-Inducible microRNAs, miR-192 and miR-215
Georges et al.
Cancer Res. 2008;68:10105-10112.
ABSTRACT | FULL TEXT  

miR-192 Regulates Dihydrofolate Reductase and Cellular Proliferation through the p53-microRNA Circuit
Song et al.
Clin. Cancer Res. 2008;14:8080-8086.
ABSTRACT | FULL TEXT  

The Emergent Role of MicroRNAs in Molecular Diagnostics of Cancer
Tam
J. Mol. Diagn. 2008;10:411-414.
ABSTRACT | FULL TEXT  

MicroRNA-21 Targets Sprouty2 and Promotes Cellular Outgrowths
Sayed et al.
Mol. Biol. Cell 2008;19:3272-3282.
ABSTRACT | FULL TEXT  

MicroRNA Expression in Colon Adenocarcinoma
Kida and Han
JAMA 2008;299:2628-2628.
FULL TEXT  

MicroRNA Signatures as Diagnostic and Therapeutic Targets
Waldman and Terzic
Clin. Chem. 2008;54:943-944.
FULL TEXT  

MicroRNAs and Colon Cancer
JWatch Gastroenterology 2008;2008:1-1.
FULL TEXT  

All you need to read in the other general journals
BMJ 2008;336:300-301.
FULL TEXT  





HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 2008 American Medical Association. All Rights Reserved.