Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer

Manish Kohli, Charles Y.F. Young, Donald J. Tindall, Debashis Nandy, Kyle M. McKenzie, Graham H. Bevan, Krishna Vanaja Donkena

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1915-1922
Number of pages8
JournalOncoTargets and Therapy
Volume8
DOIs
StatePublished - Jul 30 2015

Keywords

  • Defensin
  • Docetaxel
  • Prostate cancer
  • RNA-seq
  • Targeted RNA-seq

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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