miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.

Details

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State: Serval
Version: author
Serval ID
serval:BIB_B3039B1A6D65
Type
Article: article from journal or magazin.
Collection
Publications
Title
miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.
Journal
Plos One
Author(s)
Schou J.V., Rossi S., Jensen B.V., Nielsen D.L., Pfeiffer P., Høgdall E., Yilmaz M., Tejpar S., Delorenzi M., Kruhøffer M., Johansen J.S.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
9
Number
6
Pages
e99886
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan.
METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known.
RESULTS: After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p), were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07, Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24-2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4) in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan.
CONCLUSION: We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population.
Keywords
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Camptothecin/analogs & derivatives, Camptothecin/therapeutic use, Colorectal Neoplasms/blood, Colorectal Neoplasms/drug therapy, DNA Mutational Analysis, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Male, MicroRNAs/blood, MicroRNAs/genetics, Middle Aged, Multivariate Analysis, Mutation/genetics, Proportional Hazards Models, Proto-Oncogene Proteins/genetics, Treatment Outcome, Tumor Markers, Biological/genetics, ras Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2015 8:46
Last modification date
08/05/2019 23:58
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