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dc.contributor.author | Takahashi, Masanobu |
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dc.contributor.author | Cuatrecasas Freixas, Miriam |
dc.contributor.author | Balaguer Prunés, Francesc |
dc.contributor.author | Hur, Keun |
dc.contributor.author | Toiyama, Yuji |
dc.contributor.author | Castells Garangou, Antoni |
dc.contributor.author | Boland, C. Richard |
dc.contributor.author | Goel, Ajay |
dc.date | 2018-09-26T10:43:32Z |
dc.date | 2018-09-26T10:43:32Z |
dc.date | 2012-10-03 |
dc.date | 2018-09-26T10:43:32Z |
dc.identifier | 1932-6203 |
dc.identifier | 635324 |
dc.identifier | 23056401 |
dc.identifier.uri | http://hdl.handle.net/2445/124831 |
dc.description | 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. |
dc.format | 10 p. |
dc.format | application/pdf |
dc.language | eng |
dc.publisher | Public Library of Science (PLoS) |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0046684 |
dc.relation | PLoS One, 2012, vol. 7, num. 10, p. e46684 |
dc.relation | https://doi.org/10.1371/journal.pone.0046684 |
dc.rights | cc-by (c) Takahashi, Masanobu et al., 2012 |
dc.rights | http://creativecommons.org/licenses/by/3.0/es |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | Càncer colorectal |
dc.subject | Genètica humana |
dc.subject | Marcadors bioquímics |
dc.subject | Càncer |
dc.subject | Colorectal cancer |
dc.subject | Human genetics |
dc.subject | Biochemical markers |
dc.subject | Cancer |
dc.title | The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer |
dc.type | info:eu-repo/semantics/article |
dc.type | info:eu-repo/semantics/publishedVersion |