scholarly journals Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients

2017 ◽  
Vol 38 (8) ◽  
pp. 821-826 ◽  
Author(s):  
Yuyan Han ◽  
Junfeng Xu ◽  
Jeri Kim ◽  
Xifeng Wu ◽  
Jian Gu
2019 ◽  
Vol 41 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Junfeng Xu ◽  
Wen-Shin Chang ◽  
Chia-Wen Tsai ◽  
Da-Tian Bau ◽  
John W Davis ◽  
...  

Abstract Mitochondria play multiple important cellular functions. The purpose of this study was to evaluate whether leukocyte mitochondrial DNA copy number (mtDNAcn) is associated with aggressive prostate cancer (PCa) in African American (AA) men. We measured the mtDNAcn in peripheral blood leukocytes from 317 localized AA PCa patients and evaluated its associations with aggressive disease features at diagnosis and biochemical recurrence (BCR) after treatments. There was no significant difference in mtDNAcn among the clinical features at diagnosis, including age, prostate-specific antigen level, Gleason score and clinical stage under analysis of variance test. However, mtDNAcn was significantly associated with BCR in multivariate Cox analysis. Dichotomized into low and high mtDNAcn groups by the median value of mtDNAcn, patients with low mtDNAcn exhibited a significantly lower risk of BCR (hazard ratio = 0.32, 95% confidence interval: 0.13–0.79) compared to those with high mtDNAcn. There was a significant dose–response in tertile and quartile analyses (P for trend = 0.012 and 0.002, respectively). In Kaplan–Meier survival analyses, patients with higher mtDNAcn exhibited significantly shorter BCR-free survival time than those with lower mtDNAcn in dichotomous, tertile and quartile analyses, with long-rank P values of 0.017, 0.024 and 0.019, respectively. Our results showed for the first time that high leukocyte mtDNAcn was associated with worse prognosis in AA PCa patients.


2012 ◽  
Vol 72 (4 Supplement) ◽  
pp. C26-C26
Author(s):  
Javier Cotignola ◽  
Ahva Shahabi ◽  
Daiana B. Leonardi ◽  
Mariana C. Stern ◽  
Nora Navone ◽  
...  

2021 ◽  
Vol 10 (16) ◽  
pp. 3709
Author(s):  
Paulius Bosas ◽  
Gintaras Zaleskis ◽  
Daiva Dabkevičiene ◽  
Neringa Dobrovolskiene ◽  
Agata Mlynska ◽  
...  

Background: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. Methods: Radical prostatectomy (RP) was performed on 108 PCa stage pT2–pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. Results: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = −2.0% d−1 (AUC = 0.85 (95% CI, 0.78–0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 − CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). Conclusion: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.


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