scholarly journals Loss of HOXB13 expression in neuroendocrine prostate cancer

2020 ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immunohistochemical Staining ◽  
Prostate Adenocarcinoma ◽  
Tissue Type ◽  
Clear Cut ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Rnaseq Data ◽  
Hox Code

AbstractHOXB13, the most posterior HOX B gene, is primarily expressed in the prostate. Using immunohistochemical staining, we evaluated the expression of HOXB13 in prostatic tissues. We found that HOXB13 was expressed in both benign prostatic tissues and prostate adenocarcinoma (AdPCa) but its expression was reduced or lost in neuroendocrine prostate cancer (NEPCa). Additionally, using RNAseq data of HOXs in cell lines derived from various tissue origins, we established HOX codes for these tissue types. We applied the HOX codes to PCa samples and found that the majority of AdPCa samples sustained the prostate-specific HOX code but the majority of NEPCa samples lost it. Our analysis also showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue type. This indicates that NEPCa tumors lose prostate identity but do not gain a clear-cut new tissue identity. Finally, we treated PCa cells with all trans retinoic acid and found that the reduced/lost HOXB13 expression can be reverted, as can AR and AR targets. Taken together, our data indicate that HOXB13 expression is reduced or lost in NEPCa and a loss of prostate-specific HOX code in NEPCa represents a loss of prostatic identity.

scholarly journals Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hox Genes ◽  
Human Cancer ◽  
Specific Expression ◽  
Hox Gene ◽  
Human Cancer Cell Lines ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Hox Code ◽  
Specific Expression Pattern

AbstractHOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

scholarly journals Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Vincenza Conteduca ◽  
Sheng-Yu Ku ◽  
Luisa Fernandez ◽  
Angel Dago-Rodriquez ◽  
Jerry Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
De Novo ◽  
Genomic Analysis ◽  
Treatment Resistance ◽  
Circulating Tumor Cell ◽  
Prostate Adenocarcinoma ◽  
Neuroendocrine Prostate Cancer ◽  
Patient Heterogeneity ◽  
Tumor Cell Heterogeneity

AbstractNeuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.

Transcriptional regulation of the homeobox geneNKX3.1 by all-trans retinoic acid in prostate cancer cells

2006 ◽  
Vol 99 (5) ◽  
pp. 1409-1419 ◽  
Author(s):  
Marc A. Thomas ◽  
Myles C. Hodgson ◽  
Susan D. Loermans ◽  
Joel Hooper ◽  
Raelene Endersby ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcriptional Regulation ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Joanna Cyrta ◽  
Anke Augspach ◽  
Maria Rosaria De Filippo ◽  
Davide Prandi ◽  
Phillip Thienger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Hormonal Treatment ◽  
Prostate Adenocarcinoma ◽  
Aggressive Disease ◽  
Chromatin Remodeling Complex ◽  
Large Patient ◽  
Neuroendocrine Prostate Cancer ◽  
Specific Factors

Abstract Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10–20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors.

scholarly journals Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1405 ◽  
Author(s):  
Patel ◽  
Chugh ◽  
Tripathi
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Neuroendocrine Differentiation ◽  
Prostate Adenocarcinoma ◽  
Tumor Evolution ◽  
Aggressive Form ◽  
Neuroendocrine Prostate Cancer ◽  
Key Driver ◽  
New Perspective

Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.

scholarly journals Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Bulent Cetin ◽  
Zeynep Cetin ◽  
Suleyman Buyukberber ◽  
Ipek Isık Gonul ◽  
Ilgin Sahiner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Prostate Biopsy ◽  
Immunohistochemical Staining ◽  
Metastatic Prostate Cancer ◽  
Inguinal Lymph Node ◽  
Prostate Adenocarcinoma ◽  
Rare Manifestation ◽  
Inguinal Lymphadenopathy ◽  
Generalized Lymphadenopathy

Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

scholarly journals Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Cuijian Zhang ◽  
Jinqin Qian ◽  
Yucai Wu ◽  
Zhenpeng Zhu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Expression Profiles ◽  
Prostate Adenocarcinoma ◽  
Diagnostic Tools ◽  
Receptor Interaction ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Platinum Based Chemotherapy

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy.Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset.Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively.Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

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