Genomic analysis of castration sensitive and resistant prostate cancer patients by multiple-gene targeted sequencing.

e17525 Background: Previous studies showed the significant diversity of the genomic landscapes between castration sensitive prostate cancer (CSPC) and castration resistant prostate cancer (CRPC). AR, TP53/RB1, and BRCA2/ATM have been reported to contribute to the development of CRPC. In addition, CDK12 has recently reported to lead to the worse response to AR-targeted therapies. We are aimed to clarify the landscape of somatic gene alterations in CSPC and CRPC by multiple-gene targeted sequencing and discover the differential genes between the two treatment stages in order to guide clinical treatment. Methods: We recruited 413 prostate cancer patients including 230 CSPC and 183 CRPC. Cell-free DNA was extracted from plasma samples. Targeted sequencing of 50 genes was performed, which involved in DNA damage repair (DDR) pathway, AR pathway, TP53/RB1, etc. Chi square test or Fisher test were used to analyze the differences between two cohorts. Results: A total of 33.04% (76/230) CSPC patients carried somatic gene alterations, including 16.96% (39/230) in DDR pathway, 19.57% (45/230) in AR pathway and 7.39% (17/230) in TP53/RB1. The most frequent altered gene in CSPC was FOXA1 (9.13%,21/230), followed by NCOR2 (6.52%,15/230) and TP53 (5.65%,13/230). For CRPC patients, 66.67% (122/183) carried somatic gene alterations, including 44.81% (82/230) in DDR pathway, 49.73% (91/230) in AR pathway and 25.68% (47/183) in TP53/RB1. The most frequent mutated gene in CRPC was AR (33.33%,61/183), followed by FOXA1 (23.50%,43/183) and CDK12 (17.49%,32/183). Mutation frequencies of certain genes in CRPC patients were significantly higher than CSPC patients, including CDK12 (p < 0.001), BRCA2 (p = 0.006), ATM (p = 0.003), ATR (p = 0.007), AR (p < 0.001), FOXA1 (p = 0.001), SPOP (p = 0.002), ZBTB16 (p = 0.02), TP53 (p = 0.001), RB1 (p = 0.04) and PTEN (p = 0.001). Conclusions: It was the first study which explored the genomic alterations in Chinese CSPC and CRPC patients by liquid biopsy. These findings confirmed the genomic diversity between CSPC patients and CRPC patients, which could guide the individualized and precise management of prostate cancer in general practice. Furthermore, our findings indicated that somatic alterations in AR, CDK12, BRCA2, ATM and TP53/RB1 might contribute to the development of CRPC.

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Genomic analysis of castration sensitive and resistant prostate cancer patients by multiple-gene targeted sequencing

European Urology Open Science ◽

10.1016/s2666-1683(20)33173-6 ◽

2020 ◽

Vol 19 ◽

pp. e888

Author(s):

L. Fan ◽

B. Dong ◽

W. Xue

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Genomic Analysis ◽

Targeted Sequencing ◽

Multiple Gene

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Clinical and Epidemiologic Characteristics of Castration Resistant Prostate Cancer Patients in Sulaimaniyah, Iraqi Kurdistan

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2528 ◽

2020 ◽

Vol 11 (3) ◽

pp. 3675-3683

Author(s):

Khalid Anwar Hama Ghareeb ◽

Zahira Metwally Gad ◽

NohaAwad ◽

Mohammed Ibrahim Mohialdeen Gubari ◽

Jwan Jalal Rasheed shwana ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Castration Resistant Prostate Cancer ◽

Chi Square ◽

Face To Face ◽

Development Of Resistance ◽

Castration Resistant ◽

Iraqi Kurdistan ◽

Chi Square Test ◽

Epidemiologic Characteristics

Prostate cancer is prevalent among men aged over 65 and has been reported as the fourth most common cause of mortality of males all over the world. In addition to age, family history, and race, there are some lifestyle features such as diet, obesity, alcohol, and smoking are believed to play a role in its development. The present study was carried out in order to examine the clinical and epidemiologic characteristics of castration-resistant prostate cancer patients identify predictive factors for development of resistance to hormonal therapy. The present retrospective cohort study was carried out on 150 patients who were diagnosed with prostate cancer at Hiwa Cancer hospital in Sulaimania, Iraqi Kurdistan over the period of 2009-2014. Required data were collected using face-to-face or phone interviews using a questionnaire and the patients’ hospital records. The collected data were analyzed using descriptive statistics, one-sample Kolmogorov-Smirnov test, independent samples t-test, Mann Whitney test, and Pearson’s Chi-square test through SPSS 20.0.

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Faculty Opinions recommendation of Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718031002.793480659 ◽

2013 ◽

Author(s):

Michael Glode

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy

Clinical & Translational Oncology ◽

10.1007/s12094-021-02553-5 ◽

2021 ◽

Author(s):

G. Ingrosso ◽

B. Detti ◽

A. Fodor ◽

S. Caini ◽

S. Borghesi ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Targeted Therapy ◽

Cancer Patients ◽

Stereotactic Ablative Radiotherapy ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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Detection of N,N-diacetyllactosamine (LacdiNAc) containing free prostate-specific antigen for early stage prostate cancer diagnostics and for identification of castration-resistant prostate cancer patients

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2021.116156 ◽

2021 ◽

Vol 39 ◽

pp. 116156

Author(s):

Aniko Bertokova ◽

Tomas Bertok ◽

Eduard Jane ◽

Michal Hires ◽

Petra Ďubjaková ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Prostate Specific Antigen ◽

Early Stage ◽

Specific Antigen ◽

Cancer Diagnostics ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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Increased Hospitalization and Mortality from COVID-19 in Prostate Cancer Patients

Cancers ◽

10.3390/cancers13071630 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1630

Author(s):

Dimple Chakravarty ◽

Parita Ratnani ◽

Stanislaw Sobotka ◽

Dara Lundon ◽

Peter Wiklund ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Mortality Rates ◽

Mount Sinai Hospital ◽

Solid Cancer ◽

Continuous Variables ◽

Breast Cancer Patients ◽

Chi Square ◽

Hospital System ◽

Tumor Types

Background: Cancer patients with COVID-19 have a poor disease course. Among tumor types, prostate cancer and COVID-19 share several risk factors, and the interaction of prostate cancer and COVID-19 is purported to have an adverse outcome. Methods: This was a single-institution retrospective study on 286,609 patients who underwent the COVID-19 test at Mount Sinai Hospital system from March 2020 to December 2020. Chi-square/Fisher’s exact tests were used to summarize baseline characteristics of categorical data, and Mann–Whitney U test was used for continuous variables. Univariable logistic regression analysis to compare the hospitalization and mortality rates and the strength of association was obtained by the odds ratio and confidence interval. Results: This study aimed to compare hospitalization and mortality rates between men with COVID-19 and prostate cancer and those who were COVID-19-positive with non-prostate genitourinary malignancy or any solid cancer, and with breast cancer patients. We also compared our studies to others that reported the incidence and severity of COVID-19 in prostate cancer patients. Our studies highlight that patients with prostate cancer had higher susceptibility to COVID-19-related pathogenesis, resulting in higher mortality and hospitalization rates. Hospitalization and mortality rates were higher in prostate cancer patients with COVID-19 when compared with COVID-19 patients with non-prostate genitourinary (GU) malignancies.

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Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

Scientific Reports ◽

10.1038/s41598-021-87441-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Divya Bhagirath ◽

Michael Liston ◽

Theresa Akoto ◽

Byron Lui ◽

Barbara A. Bensing ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Neuroendocrine Differentiation ◽

Extracellular Vesicle ◽

Machine Learning Algorithms ◽

Castration Resistant Prostate Cancer ◽

Cellular Models ◽

Non Invasive ◽

Castration Resistant ◽

Neuroendocrine Prostate Cancer

AbstractNeuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.

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