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.
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.
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.
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.
BMC cancer. 2020 Apr 15*** epublish ***
Yoshinori Matsuda, Shintaro Narita, Taketoshi Nara, Huang Mingguo, Hiromi Sato, Atsushi Koizumi, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Takamitsu Inoue, Yuko Hiroshima, Hiroshi Nanjo, Shigeru Satoh, Norihiko Tsuchiya, Tomonori Habuchi
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan., Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. ., Department of Pathology, Akita University Hospital, Akita, Japan., Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan., Department of Urology, Yamagata University School of Medicine, Akita, Japan.