Impact of nuclear YAP1 expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer.

Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Up-Regulation*; Adaptor Proteins, Signal Transducing/*metabolism ; Docetaxel/*therapeutic use ; Neoplasm, Residual/*metabolism ; Prostatic Neoplasms/*metabolism ; Transcription Factors/*metabolism; Adaptor Proteins, Signal Transducing/genetics ; Cell Line, Tumor ; Cell Nucleus ; Cell Proliferation ; Gene Knockdown Techniques ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm, Residual/drug therapy ; Prostatic Neoplasms/drug therapy ; Survival Analysis ; Tissue Array Analysis ; Transcription Factors/genetics ; YAP-Signaling Proteins

Background: Although docetaxel-based chemohormonal therapy (CHT) is one of the standard treatments for castration-resistant prostate cancer (CRPC), pertinent biomarkers and precise mechanisms involved in the resistance for CHT for CRPC remain unknown. We investigated the relationship between chemohormonal resistance and the expression of steroid receptors and Hippo pathway proteins using a docetaxel-resistant prostate cancer (PCa) cell line and human PCa tissues in patients who underwent surgery with and without neoadjuvant therapy.
Methods: A docetaxel-resistant subline (22Rv1-DR) was generated to assess Hippo pathway protein expression and the effect of YAP1 inhibition on cellular characteristics. A tissue microarray with 203 cores from 70 high-risk localized PCa tissues was performed to assess steroid receptor and Hippo pathway protein expressions.
Results: Nuclear YAP (nYAP) expression was higher in 22RV-1-DR than in parental 22Rv-1 and YAP1 knockdown suppressed cell proliferation of 22Rv1-DR. Steroid receptor and Hippo pathway protein expressions varied among three different neoadjuvant groups, and nYAP1 expression was the highest in the CHT group. The patients with high nYAP in residual cancer after neoadjuvant CHT had a significantly higher biochemical recurrence (BCR) rate than those with low nYAP1. On multivariate analysis, the high nYAP1 was an independent prognostic factor for BCR.
Conclusions: nYAP expression is a potential biomarker in high-risk patients treated with docetaxel-based CHT. Steroid receptors and Hippo pathway proteins may play a role in the chemohormonal resistance in advanced PCa.

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Keywords: Docetaxel; High-risk; Neoadjuvant chemohormonal therapy; Prostate cancer; Residual cancer; YAP1

0 (Adaptor Proteins, Signal Transducing)
0 (Transcription Factors)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)
15H5577CQD (Docetaxel)

Date Created: 20200416 Date Completed: 20201218 Latest Revision: 20211204

20250114

PMC7333261

10.1186/s12885-020-06844-y

32293349