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Article: Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma

TitleAssociation of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2009, v. 15 n. 18, p. 5878-5887 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/65484
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
PubMed Central ID
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorSchetter, AJen_HK
dc.contributor.authorGiang, HNen_HK
dc.contributor.authorBowman, EDen_HK
dc.contributor.authorMathé, EAen_HK
dc.contributor.authorSiu, TYen_HK
dc.contributor.authorHawkes, JEen_HK
dc.contributor.authorCroce, CMen_HK
dc.contributor.authorSuet, YLen_HK
dc.contributor.authorHarris, CCen_HK
dc.date.accessioned2010-08-11T08:22:27Z-
dc.date.available2010-08-11T08:22:27Z-
dc.date.issued2009en_HK
dc.identifier.citationClinical Cancer Research, 2009, v. 15 n. 18, p. 5878-5887en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65484-
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.en_HK
dc.languageeng-
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofClinical Cancer Researchen_HK
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 adenocarcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=15&issue=18&spage=5878&epage=5887&date=2009&atitle=Association+of+inflammation-related+and+microRNA+gene+expression+with+cancer+specific+mortality+of+colon+adenocarcinoma-
dc.identifier.emailSuet, YL:suetyi@hkucc.hku.hken_HK
dc.identifier.authoritySuet, YL=rp00359en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-09-0627en_HK
dc.identifier.pmid19737943-
dc.identifier.pmcidPMC2745503-
dc.identifier.scopuseid_2-s2.0-70349454207en_HK
dc.identifier.hkuros174351-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349454207&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue18en_HK
dc.identifier.spage5878en_HK
dc.identifier.epage5887en_HK
dc.identifier.isiWOS:000269982800032-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike6594477-

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