ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients
Abstract Background Aldehyde dehydrogenase 1A3 (ALDH1A3) has been implicated in the survival and proliferation of prostate cancer cells. Methods We retrospectively reviewed our patients with advanced disease on adjuvant hormonal therapy after prostatectomy. Time to castration resistance stage was do...
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doaj-069cf4e1f701475c90ead6321cc9a5a72020-11-25T02:09:21ZengBMCBMC Cancer1471-24072020-05-012011810.1186/s12885-020-06899-xALDH1A3 serves as a predictor for castration resistance in prostate cancer patientsShangqian Wang0Xiang Zhou1Chao Liang2Meiling Bao3Ye Tian4Jundong Zhu5Tongtong Zhang6Jie Yang7Zengjun Wang8Department of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The Third Affiliated Hospital of Soochow University, The First People’s Hospital of ChangzhouDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Aldehyde dehydrogenase 1A3 (ALDH1A3) has been implicated in the survival and proliferation of prostate cancer cells. Methods We retrospectively reviewed our patients with advanced disease on adjuvant hormonal therapy after prostatectomy. Time to castration resistance stage was documented. And Immunohistochemistry analysis for ALDH1A3 was performed for those patient samples on tissue microarray. Bioinformatics anslysis was used for RNA sequencing data of both primary prostate cancer and metastatic castration resistance prostate cancer (mCRPC) from online datasets. Crispr-Cas9 was used to knock out ALDH1A3 in prostate cancer luminal cells, and morphologic analysis as well as the Gene Set Enrichment Analysis (GSEA) were facilitated to discover the mechanisms of the resistance phenotype. Results We found that the patients with ALDH1A3 low expression had shorter time to progression to castration resistance compared with those of higher expression group on adjuvant hormonal therapy after radical prostatectomy. The ALDH1A3 knockout cells gradually acquired resistance to androgen deprivation therapy, a few cells have been found in knockout group showing as that the spindle-like luminal cells in charcoal stripped medium. Furthermore, PI3K pathway activation has been confirmed by Western blot. The PI3K pathway inhibitor BEZ235 has been demonstrated that the acquired ADT resistance by ALDH1A3 down regulation could be rescued by PI3K pathway inhibitor. Conclusion These results suggested a novel function for ALDH1A3 in development of mCRPC, and indicated PI3K pathway inhibitor has the potential in the treatment of a subgroup of mCRPC patients.http://link.springer.com/article/10.1186/s12885-020-06899-xCastration resistance prostate cancerSurvival timeAldehyde dehydrogenaseAndrogen deprivation therapyResistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shangqian Wang Xiang Zhou Chao Liang Meiling Bao Ye Tian Jundong Zhu Tongtong Zhang Jie Yang Zengjun Wang |
spellingShingle |
Shangqian Wang Xiang Zhou Chao Liang Meiling Bao Ye Tian Jundong Zhu Tongtong Zhang Jie Yang Zengjun Wang ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients BMC Cancer Castration resistance prostate cancer Survival time Aldehyde dehydrogenase Androgen deprivation therapy Resistance |
author_facet |
Shangqian Wang Xiang Zhou Chao Liang Meiling Bao Ye Tian Jundong Zhu Tongtong Zhang Jie Yang Zengjun Wang |
author_sort |
Shangqian Wang |
title |
ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients |
title_short |
ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients |
title_full |
ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients |
title_fullStr |
ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients |
title_full_unstemmed |
ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients |
title_sort |
aldh1a3 serves as a predictor for castration resistance in prostate cancer patients |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-05-01 |
description |
Abstract Background Aldehyde dehydrogenase 1A3 (ALDH1A3) has been implicated in the survival and proliferation of prostate cancer cells. Methods We retrospectively reviewed our patients with advanced disease on adjuvant hormonal therapy after prostatectomy. Time to castration resistance stage was documented. And Immunohistochemistry analysis for ALDH1A3 was performed for those patient samples on tissue microarray. Bioinformatics anslysis was used for RNA sequencing data of both primary prostate cancer and metastatic castration resistance prostate cancer (mCRPC) from online datasets. Crispr-Cas9 was used to knock out ALDH1A3 in prostate cancer luminal cells, and morphologic analysis as well as the Gene Set Enrichment Analysis (GSEA) were facilitated to discover the mechanisms of the resistance phenotype. Results We found that the patients with ALDH1A3 low expression had shorter time to progression to castration resistance compared with those of higher expression group on adjuvant hormonal therapy after radical prostatectomy. The ALDH1A3 knockout cells gradually acquired resistance to androgen deprivation therapy, a few cells have been found in knockout group showing as that the spindle-like luminal cells in charcoal stripped medium. Furthermore, PI3K pathway activation has been confirmed by Western blot. The PI3K pathway inhibitor BEZ235 has been demonstrated that the acquired ADT resistance by ALDH1A3 down regulation could be rescued by PI3K pathway inhibitor. Conclusion These results suggested a novel function for ALDH1A3 in development of mCRPC, and indicated PI3K pathway inhibitor has the potential in the treatment of a subgroup of mCRPC patients. |
topic |
Castration resistance prostate cancer Survival time Aldehyde dehydrogenase Androgen deprivation therapy Resistance |
url |
http://link.springer.com/article/10.1186/s12885-020-06899-x |
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