scholarly journals USP44 Promoter Methylation in Plasma Cell-Free DNA in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4607
Author(s):  
Dora Londra ◽  
Sophia Mastoraki ◽  
Evangelos Bournakis ◽  
Martha Zavridou ◽  
Anastasios Thanos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real Time ◽  
Plasma Cell ◽  
Promoter Methylation ◽  
Metastatic Prostate Cancer ◽  
Response To Therapy ◽  
Tumor Evolution ◽  
Cell Free Dna ◽  
Free Dna ◽  
First Time

Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). USP44 is a critical gene which plays an important role in cell proliferation; however, its accurate role in other cellular networks is under research. USP44 promoter methylation has been so far reported in colorectal neoplasia and metastatic breast cancer. In this study, we examined for the first time USP44 promoter methylation in plasma cell-free DNA (cfDNA) of patients with prostate cancer (early stage n = 32, metastatic n = 39) and 10 healthy donors (HD). USP44 promoter methylation was detected in plasma cell-free DNA by a newly developed highly specific and sensitive real-time MSP method. Our findings indicate that USP44 promoter is methylated in plasma cell-free DNA of metastatic prostate cancer patients and that detection of USP44 promoter methylation is significantly associated with overall survival (OS) (p = 0.008). We report for the first time that detection of USP44 promoter methylation in plasma cell free DNA provides significant prognostic information in metastatic prostate cancer.

Impact Of Cell-Free Plasma DNA In Metastatic And Non-Metastatic Prostate Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Abdelraouf A. Abonar ◽  
Shymaa E. Ayoub ◽  
Ibrahim A. Tagreda ◽  
Marwa N. Abdelhafez ◽  
Mohammed M Khamiss ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Metastatic Prostate Cancer ◽  
Plasma Dna ◽  
Cell Free Dna ◽  
Group Iii ◽  
Free Dna ◽  
Group I ◽  
Total Psa ◽  
Free Plasma

: Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. Our study aims at assessing the use of Cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. The study included 180 subjects who were classified into four groups: Group I (GI) included 50 in perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were done for all groups. Our study revealed that the level of tPSA was significantly higher in prostate cancer patients while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of the group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. There was a statistically significant difference in yields of cfDNA between metastatic and non- metastatic groups (P=0.03) with a higher level in the metastatic group.

scholarly journals Cell-Free DNA Alterations in the AR Enhancer and Locus Predict Resistance to AR-Directed Therapy in Patients With Metastatic Prostate Cancer

2020 ◽  
pp. 680-713 ◽  
Author(s):  
Ha X. Dang ◽  
Pradeep S. Chauhan ◽  
Haley Ellis ◽  
Wenjia Feng ◽  
Peter K. Harris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Metastatic Prostate Cancer ◽  
Progression Free Survival ◽  
Therapy Resistance ◽  
Cancer Resistance ◽  
Liquid Biopsies ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna

PURPOSE Cell-free DNA (cfDNA) and circulating tumor cell (CTC)–based liquid biopsies have emerged as potential tools to predict responses to androgen receptor (AR)–directed therapy in metastatic prostate cancer. However, because of complex mechanisms and incomplete understanding of genomic events involved in metastatic prostate cancer resistance, current assays (eg, CTC AR-V7) demonstrate low sensitivity and remain underutilized. The recent discovery of AR enhancer amplification in > 80% of patients with metastatic disease and its association with disease resistance presents an opportunity to improve on current assays. We hypothesized that tracking AR/enhancer genomic alterations in plasma cfDNA would detect resistance with high sensitivity and specificity. PATIENTS AND METHODS We developed a targeted sequencing and analysis method as part of a new assay called Enhancer and Neighboring Loci of Androgen Receptor Sequencing (EnhanceAR-Seq). We applied EnhanceAR-Seq to plasma collected from 40 patients with metastatic prostate cancer treated with AR-directed therapy to monitor AR/enhancer genomic alterations and correlated these events with therapy resistance, progression-free survival (PFS), and overall survival (OS). RESULTS EnhanceAR-Seq identified genomic alterations in the AR/enhancer locus in 45% of cases, including a 40% rate of AR enhancer amplification. Patients with AR/enhancer alterations had significantly worse PFS and OS than those without (6-month PFS, 30% v 71%; P = .0002; 6-month OS, 59% v 100%; P = .0015). AR/enhancer alterations in plasma cfDNA detected 18 of 23 resistant cases (78%) and outperformed the CTC AR-V7 assay, which was also run on a subset of patients. CONCLUSION cfDNA-based AR locus alterations, including of the enhancer, are strongly associated with resistance to AR-directed therapy and significantly worse survival. cfDNA analysis using EnhanceAR-Seq may enable more precise risk stratification and personalized therapeutic approaches for metastatic prostate cancer.

Association of plasma cell-free DNA concentration [cfDNA] with outcome from taxane therapy (TT) for castration resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5014-5014 ◽  
Author(s):  
Niven Mehra ◽  
Rossitza Christova ◽  
Lorna Pope ◽  
Suzanne Carreira ◽  
Jane Goodall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Castration Resistant Prostate Cancer ◽  
Cell Free Dna ◽  
Dna Concentration ◽  
Castration Resistant ◽  
Free Dna

Plasma cell free DNA (cfDNA) based somatic aberrations detected in treatment naïve metastatic hormone sensitive prostate cancer (mHSPC), hormonally ablated mHSPC and metastatic castration resistant prostate cancer (mCRPC) states and their impact on survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5047-5047
Author(s):  
Manish Kohli ◽  
Winston Tan ◽  
Tiantian Zheng ◽  
Amy Wang ◽  
Calvin Wong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Copy Number Variations ◽  
Cell Free Dna ◽  
Androgen Ablation ◽  
Free Dna ◽  
Impact On Survival ◽  
Treatment Naïve ◽  
The Impact ◽  
Somatic Aberrations

5047 Background: We identified plasma cell free DNA (cfDNA) based copy number variations (CNV); single nucleotide variants (SNVs) & TMPRSS-ERG fusion in four sub states of metastatic prostate cancer (mPCa) and determined the impact on survival. Two mHSPC cohorts included treatment naïve, gp-1 and mHSPC patients (pts) responding to chronic androgen ablation (AA) (gp-2). Two mCRPC cohorts included mHSPC pts with PSA relapse on chronic AA (gp-3) and a clinically progressive mCRPC cohort post AA (gp-4). Methods: Enrollment of mPCa pts was performed from 2009-14 who were followed until 2018. Plasma from collected blood was used for extracting cfDNA. NGS was performed using Illumina HiSeq X for a preselected target panel of 129 genes including DNA damage repair genes. Statistical analyses of genomic aberrations were performed in R 3.5.1 and Cox proportional-hazard models were used for survival analyses. Results: A total of 255 pts were enrolled with 215 having adequate cfDNA that passed NGS QC. Median study follow up was 90.2 (Range:73;99) months. The table highlights pts in each gp with CNV, SNV, fusion events. ARamplification was higher in mCRPC gps3&4 (20/103 pts) compared to 3/106 pts in mHSPC gps1&2 (p < 0.001) and was prognostic for poor survival in mCRPC (p < 0.001;HR:3.34; 95%CI: 1.9-5.76). 54/103 pts in gp3&4 had SNVs in TP53 compared to 34/106 pts in mHSPC gps1&2 (P < 0.01). SNVs in APC, AR, CDK12 and BRIP1 were also increased in gps3&4 (p < 0.01). Gp1 mHSPC pts with SNVs in ATM/ CHEK2 had shorter response to AA (p < 0.001; HR:3.66; 95%: CI:1.81-7.39). Conclusions: Plasma cfDNA based somatic aberrations are detected with increased prevalence in mHSPC to mCRPC states. The ease of specimen collection and the need for molecular profiling in mPCa increases its potential for clinical applications in pt care. [Table: see text]

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