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Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by -hypoxia inducible factors- that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression. Gene expression was quantified by RT-qPCR in a retrospective series of 32 patients with invasive ductal carcinoma. Data were analyzed in relation to classical clinicopathological criteria and relapse occurrence. Coordinated overexpression of selected genes was observed in high-grade and HER2+ tumors. Hierarchical cluster analysis of gene expression significantly segregated relapsed patients p = 0.008, Chi2 test. All genes except one were up-regulated and six markers were significantly expressed in tumors from recurrent patients. The expression of this 6-gene set was used to develop a basic algorithm for identifying recurrent patients according to a risk score of relapse. Analysis of Kaplan-Meier relapse-free survival curves allowed the definition of a threshold score of 2 p = 0.021, Mantel-Haenszel test. The risk of recurrence was increased by 40% in patients with a high score. In addition to classical prognostic factors, we showed that hypoxic markers have potential prognostic value for outcome and late recurrence prediction, leading to improved treatment decision-making for patients with early-stage invasive breast cancer. It will be necessary to validate the clinical relevance of this prognostic approach through independent studies including larger prospective patient cohorts.



Autor: Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault

Fuente: http://plos.srce.hr/



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