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Article: Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma
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TitleAssociation of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma
 
AuthorsSchetter, AJ1
Giang, HN1 3
Bowman, ED1
Mathé, EA1
Siu, TY4
Hawkes, JE1 3
Croce, CM2
Suet, YL4
Harris, CC1
 
Issue Date2009
 
PublisherAmerican Association for Cancer Research.
 
CitationClinical Cancer Research, 2009, v. 15 n. 18, p. 5878-5887 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-09-0627
 
AbstractPurpose: Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression. Experimental Design: Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression. Results: PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (|Z-score| >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this micro-RNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone. Conclusion: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients. © 2009 American Association for Cancer Research.
 
ISSN1078-0432
2013 Impact Factor: 8.193
2013 SCImago Journal Rankings: 5.150
 
DOIhttp://dx.doi.org/10.1158/1078-0432.CCR-09-0627
 
PubMed Central IDPMC2745503
 
ISI Accession Number IDWOS:000269982800032
Funding AgencyGrant Number
Intramural Research Program of the National Cancer Institute
Center for Cancer Research, NIH
Cancer Prevention Fellowship Program, Office of the Director, National Cancer Institute, NIH
Howard Hughes Medical Institute
Funding Information:

Grant support: Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH. A.J. Schetter was supported by the Cancer Prevention Fellowship Program, Office of the Director, National Cancer Institute, NIH. G.H. Nguyen and J.E. Hawkes were supported by the Howard Hughes Medical Institute Grant for Graduate Medical Education.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSchetter, AJ
 
dc.contributor.authorGiang, HN
 
dc.contributor.authorBowman, ED
 
dc.contributor.authorMathé, EA
 
dc.contributor.authorSiu, TY
 
dc.contributor.authorHawkes, JE
 
dc.contributor.authorCroce, CM
 
dc.contributor.authorSuet, YL
 
dc.contributor.authorHarris, CC
 
dc.date.accessioned2010-08-11T08:22:27Z
 
dc.date.available2010-08-11T08:22:27Z
 
dc.date.issued2009
 
dc.description.abstractPurpose: Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression. Experimental Design: Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression. Results: PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (|Z-score| >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this micro-RNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone. Conclusion: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients. © 2009 American Association for Cancer Research.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationClinical Cancer Research, 2009, v. 15 n. 18, p. 5878-5887 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-09-0627
 
dc.identifier.citeulike6594477
 
dc.identifier.doihttp://dx.doi.org/10.1158/1078-0432.CCR-09-0627
 
dc.identifier.epage5887
 
dc.identifier.hkuros174351
 
dc.identifier.isiWOS:000269982800032
Funding AgencyGrant Number
Intramural Research Program of the National Cancer Institute
Center for Cancer Research, NIH
Cancer Prevention Fellowship Program, Office of the Director, National Cancer Institute, NIH
Howard Hughes Medical Institute
Funding Information:

Grant support: Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH. A.J. Schetter was supported by the Cancer Prevention Fellowship Program, Office of the Director, National Cancer Institute, NIH. G.H. Nguyen and J.E. Hawkes were supported by the Howard Hughes Medical Institute Grant for Graduate Medical Education.

 
dc.identifier.issn1078-0432
2013 Impact Factor: 8.193
2013 SCImago Journal Rankings: 5.150
 
dc.identifier.issue18
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2745503
 
dc.identifier.pmid19737943
 
dc.identifier.scopuseid_2-s2.0-70349454207
 
dc.identifier.spage5878
 
dc.identifier.urihttp://hdl.handle.net/10722/65484
 
dc.identifier.volume15
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research.
 
dc.publisher.placeUnited States
 
dc.relation.ispartofClinical Cancer Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdenocarcinoma - diagnosis - genetics - mortality
 
dc.subject.meshColonic Neoplasms - diagnosis - genetics - mortality
 
dc.subject.meshInflammation - genetics
 
dc.subject.meshMicroRNAs - genetics
 
dc.subject.meshTumor Markers, Biological - genetics
 
dc.titleAssociation of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. National Cancer Institute
  2. Ohio State University Comprehensive Cancer Center
  3. Howard Hughes Medical Institute
  4. The University of Hong Kong