Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer
نویسندگان
چکیده
This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration-resistant prostate cancer (CRPC). RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing) before and after docetaxel treatment using the Illumina's HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two-fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5). In addition, post-docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8). Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3 RNA transcripts in blood prior to treatment will be helpful to determine which patients are better candidates to receive docetaxel chemotherapy.
منابع مشابه
A Systematic Review of Clinical Practice Guidelines for Castration-Resistant Prostate Cancer
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Cancer constitutes a huge burden on societies in countries with any level of economic development. Prostate cancer is the first most diagnosed cancer of men in developed countries and the forth one in developing countries in terms of incidence rate. It is also the third incident cancer of men in Iran along with a prevalence of about 10,000 cases. Castration-resistant prostate cancer (CRPC) is a...
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Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy
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عنوان ژورنال:
دوره 8 شماره
صفحات -
تاریخ انتشار 2015