scholarly journals Genome-wide association study of germline copy number variations reveals an association with prostate cancer aggressiveness

Mutagenesis ◽  
2020 ◽  
Vol 35 (3) ◽  
pp. 283-290
Author(s):  
Stefanie Brezina ◽  
Moritz Feigl ◽  
Tanja Gumpenberger ◽  
Ricarda Staudinger ◽  
Andreas Baierl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Copy Number ◽  
Copy Number Variations ◽  
Prostatic Hyperplasia ◽  
Aggressive Prostate Cancer ◽  
Genome Wide ◽  
Cancer Aggressiveness

Abstract Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.

scholarly journals Nanoscale flow cytometry of patient plasma for the detection of prostate cancer-associated extracellular vesicles

2017 ◽  
Vol 3 (2) ◽  
pp. 1-2 ◽  
Author(s):  
Andrew C. Poon ◽  
Johanna Garzon ◽  
Sabine Brett ◽  
Matthew Lowerison ◽  
Karla Williams ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Flow Cytometry ◽  
Benign Prostatic Hyperplasia ◽  
Cancer Patients ◽  
Extracellular Vesicles ◽  
Specific Antigen ◽  
Prostatic Hyperplasia ◽  
Submicron Particles ◽  
Screening Tests ◽  
Positive Events

Introduction Prostate cancer is the predominant cancer in men, affecting one in seven men during their lifetime. Current tests for prostate cancer include the digital rectal exam and the prostate-specific antigen (PSA) test. Extracellular vesicles (EVs) are submicron particles that participate in intercellular cross-talk by releasing cell mediators such as microRNA, carbohydrates and proteins. While they are known to express the broad tetraspanin family of proteins, i.e. CD9/CD63, prostate cancer-derived EVs have also been found to express PSA and six transmembrane epithelial antigen of the prostate (STEAP1). Traditionally, scientists have purified these EVs through ultracentrifugation. Here we propose a tandem purification of patient plasma, followed by nanoscale flow cytometry (A50+) as a novel method to detect tumour-derived EVs. Materials and Methods Plasma was obtained from healthy volunteers, patients with benign prostatic hyperplasia (BPH), and patients with metastatic prostate cancer. CD9, CD63, PSA and STEAP1 were used as primary antibodies for the purification of EVs from neat plasma. To perform the purification in tandem, Protein G immunoprecipitation using CD9 and PSA was carried out first, followed by immunoaffinity purification with biotinylated CD63 and STEAP1. First and second elutions were collected for the enumeration of dual positive events by A50+. Initial histogram overlays and bivariate plots of neat and purified plasma were computed, then exported as comma-separated values for mathematical modelling by MATLAB. Results Strong dual positive EV populations from patient plasma were optimised, demonstrating that the method enriches tumour-derived EVs from neat samples of patient plasma. This was observed for HVs, patients with benign prostatic hyperplasia, and prostate cancer patients with Gleason 4+4. Enrichment in these purified samples was measured by A50+ and demonstrated by overlaying purified and non-purified histoplots by MATLAB. Additional results show that PSA and STEAP1 can be adapted to detect single or dual positive populations of tumour-associated EVs in prostate cancer patients. Discussions and Conclusions This study suggests that tandem purification of tumour-associated EVs and A50+ analysis from plasma of prostate cancer patients can lead to earlier diagnosis and risk stratification, compared to traditional screening tests and aspiration cytology. Future studies will be directed toward optimizing this detection method for markers of other cancer types to achieve better outcomes in cancer detection and prognosis.

scholarly journals Exploring Prostate Cancer Patients’ Interest and Preferences for Receiving Genetic Risk Information About Cancer Aggressiveness

2020 ◽  
Vol 14 (3) ◽  
pp. 155798832091962
Author(s):  
Siddhartha Roy ◽  
Clement K. Gwede ◽  
Teri L. Malo ◽  
Courtney L. Scherr ◽  
Selina Radlein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Treatment Option ◽  
Genetic Risk ◽  
Risk Information ◽  
Future Research ◽  
Aggressive Prostate Cancer ◽  
Genetic Risk Information ◽  
Cancer Aggressiveness ◽  
To Receive

The number of cases of aggressive prostate cancer is increasing. Differentiating between aggressive and indolent cases has resulted in increased difficulty for the physician and patient to decide on the best treatment option. Due to this challenge, efforts are underway to profile genetic risk for prostate cancer aggressiveness, which may help physicians and patients at risk for developing aggressive prostate cancer to select an appropriate treatment option. This study explores patients’ interest in receiving genetic results, preference for how genetic risk information should be communicated, and willingness to share results with adult male first-degree relatives (FDRs). A nine-item survey was adapted to assess their beliefs and attitudes about genetic testing for prostate cancer aggressiveness. In addition, participants ( n = 50) responded to hypothetical scenarios and questions associated with perceived importance of risk disclosure, preferences for receiving genetic risk information, and sharing of results with FDRs. As the hypothetical risk estimate for aggressive prostate cancer increased, patients’ willingness to receive genetic risk information increased. This study found that most patients preferred receiving genetic risk education in the form of a DVD (76%), one-page informational sheet (75%), or educational booklet (70%). Almost all patients (98%) reported that they would be willing to share their test results with FDRs. The results of this study highlight prostate cancer patients’ desire to receive and share genetic risk information. Future research should focus on assessing the long-term benefits of receiving genetic information for prostate cancer patients and implications of sharing this information with FDRs.

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