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Title: The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer
Author: Takahashi, Masanobu
Cuatrecasas Freixas, Miriam
Balaguer, Francesc
Hur, Keun
Toiyama, Yuji
Castells Garangou, Antoni
Boland, C. Richard
Goel, Ajay
Keywords: Càncer colorectal
Genètica humana
Marcadors bioquímics
Colorectal cancer
Human genetics
Biochemical markers
Issue Date: 3-Oct-2012
Publisher: Public Library of Science (PLoS)
Abstract: Aim: Development of robust prognostic and/or predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of certain miRNAs might have prognostic/predictive value in CRC patients treated with conventional cytotoxic chemotherapies. Methods: We studied a cohort of 273 CRC specimens from stage II/III patients treated with 5-fluorouracil-based adjuvant chemotherapy and stage IV patients subjected to 5-fluorouracil and oxaliplatin-based chemotherapy. In a screening set (n = 44), 13 of 21 candidate miRNAs were successfully quantified by multiplex quantitative RT-PCR. In the validation set comprising of the entire patient cohort, miR-148a expression status was assessed by quantitative RT-PCR, and its promoter methylation was quantified by bisulfite pyrosequencing. Lastly, we analyzed the associations between miR-148a expression and patient survival. Results: Among the candidate miRNAs studied, miR-148a expression was most significantly down-regulated in advanced CRC tissues. In stage III and IV CRC, low miR-148a expression was associated with significantly shorter disease free-survival (DFS), a worse therapeutic response, and poor overall survival (OS). Furthermore, miR-148a methylation status correlated inversely with its expression, and was associated with worse survival in stage IV CRC. In multivariate analysis, miR-148a expression was an independent prognostic/predictive biomarker for advanced CRC patients (DFS in stage III, low vs. high expression, HR 2.11; OS in stage IV, HR 1.93). Discussion: MiR-148a status has a prognostic/predictive value in advanced CRC patients treated with conventional chemotherapy, which has important clinical implications in improving therapeutic strategies and personalized management of this malignancy.
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It is part of: PLoS One, 2012, vol. 7, num. 10, p. e46684
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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