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Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin

Jiang, J and Zheng, X and Xu, X and Zhou, Q and Yan, H and Zhang, X and Lu, B and Wu, C and Ju, J (2011) Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin. PLoS ONE, 6 (8).

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Abstract

Background: The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens. Experimental Design: Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m 2/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m 2/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis. Results: The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens. Conclusion: Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer. © 2011 Jiang et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jiang, J
Zheng, X
Xu, X
Zhou, Q
Yan, H
Zhang, X
Lu, Bbinfeng@pitt.eduBINFENG
Wu, C
Ju, J
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBlagosklonny, Mikhail V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 24 August 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0023271
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
MeSH Headings: Antineoplastic Agents--pharmacology; Antineoplastic Agents--therapeutic use; Antineoplastic Combined Chemotherapy Protocols--pharmacology; Antineoplastic Combined Chemotherapy Protocols--therapeutic use; Drug Combinations; Female; Floxuridine--pharmacology; Floxuridine--therapeutic use; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; MicroRNAs--genetics; MicroRNAs--metabolism; Middle Aged; Organoplatinum Compounds--pharmacology; Organoplatinum Compounds--therapeutic use; Oxonic Acid--pharmacology; Oxonic Acid--therapeutic use; Prognosis; Stomach Neoplasms--diagnosis; Stomach Neoplasms--drug therapy; Stomach Neoplasms--genetics; Tegafur--pharmacology; Tegafur--therapeutic use; Treatment Outcome
Other ID: NLM PMC3158077
PubMed Central ID: PMC3158077
PubMed ID: 21876743
Date Deposited: 05 Sep 2012 19:04
Last Modified: 22 Dec 2018 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13889

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