Promoter Methylation of Protocadherin8 is an Independent Prognostic Factor for Biochemical Recurrence of Early-Stage Prostate Cancer

Niu, Wenbin; Gui, Shi-Liang; Lin, Ying‐Li; Fu, Xingli; Ma, Jun

doi:10.12659/msm.893083

Cited by 13 publications

(10 citation statements)

References 27 publications

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“…Previous reports indicated that PCDH8 functions as a tumor suppressor and is often silenced by aberrant promoter methylation in human cancers, including prostate cancer [ 15 – 18 ]. In our previous study, we confirmed that PCDH8 was often methylated in prostate cancer tissues, and was correlated with malignant behaviors and poor outcome of the disease [ 19 ]. However, little is known about the clinical significance of PCDH8 methylation in serum of prostate cancer, especially in low Gleason score cases.…”

Section: Introductionsupporting

confidence: 58%

Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

Lin

2017

Med Sci Monit

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BackgroundPCDH8 is a newly-discovered suppressor gene that is frequently inactivated by aberrant methylation in several human cancers, including prostate cancer. The identification of PCDH8 methylation can be used as a potential predictive biomarker. Prostate cancer patients with high Gleason score are considered as being at high risk for tumor recurrence and progression, and adjuvant therapy is often routinely performed in clinical practice. In the present study, we did not measure the methylation of PCDH8 in these patients. The main purpose of the present study was to evaluate the clinical significance of PCDH8 methylation in serum of prostate cancer patients with low Gleason score.Material/MethodsPCDH8 methylation in serum samples of 117 patients and 47 controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8 methylation status with the clinicopathological parameters of prostate cancer patients with low Gleason score and patient outcomes.ResultsWe found that PCDH8 was more frequently methylated in serum samples of patients with prostate cancer than in controls. PCDH8 methylation was correlated with advanced clinical stage (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse biochemical recurrence (BCR)-free survival (P<0.001) than patients without. Independent prognostic factors for worse BCR-free survival of prostate cancer patients with low Gleason score were: PCDH8 methylation in serum (Exp (B)=3.147, 95% CI: 1.152–7.961, P=0.007), clinical stage (Exp (B)=2.53, 95% CI: 1.032–4.763, P=0.025) and lymph node status (Exp (B)=1.476, 95% CI: 1.107–4.572, P=0.042).ConclusionsOur study indicated that PCDH8 methylation in serum occurred frequently in prostate cancer patients and was correlated with risk factors for poor outcome. The methylation of PCDH8 in serum is a potential predictive marker for prostate cancer patients with low Gleason score after surgery.

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Section: Introductionsupporting

confidence: 58%

Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

Lin

2017

Med Sci Monit

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“…The PCDH8 gene promoter is frequently methylated in renal cell carcinoma (~58%), which suggests that it could act as a tumor suppressor or that its tumor suppressor activity is down-modulated in the methylated state (37, 38). Moreover, several studies report that the epigenetic inactivation of PCDH8 by promoter methylation is associated with the loss of its tumor-suppressive function in human nasopharyngeal carcinoma (39), gastric cancer (40), bladder cancer (41), and prostate cancer (42). However, it is unknown the status of PCDH8 expression in gliomas.…”

Section: Discussionmentioning

confidence: 99%

miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis

Xue

Zhou

et al. 2016

Cancer Research

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Malignant glioma is an often fatal type of cancer. Aberrant activation of STAT3 leads to glioma tumorigenesis. STAT3- induced transcription of protein-coding genes has been extensively studied; however, little is known about STAT3-regulated miRNA gene transcription in glioma tumorigenesis. In this study, we found that abnormal activation or decreased expression of STAT3 promotes or inhibits the expression of miR-182- 5p, respectively. Bioinformatics analyses determined that tumor suppressor protocadherin-8 (PCDH8) is a candidate target gene of miR-182-5p. miR-182-5p negatively regulated PCDH8 expression by directly targeting its 3'-untranslated region. PCDH8 knockdown induced the proliferative and invasive capacities of glioma cells. Silencing of PCDH8 or miR-182-5p mimics could reverse the inhibitory effect of WP1066, a STAT3 inhibitor, or STAT3 knockdown in vitro and in vivo on glioma progression. Clinically, expression levels of PCDH8 were inversely correlated with those of p- STAT3 or miR-182-5p in glioblastoma tissues. These findings reveal that the STAT3/miR-182-5p/PCDH8 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioma.

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“…For BCR-free survival analysis, Kaplan-Meier survival analysis was used and the differences in survival were analyzed using the log-rank test. Univariate and multivariate Cox regression analysis was used to evaluate the predictive effect of PCDH17 methylation in prostate cancer [ 30 ]. The a priori sample size was calculated and power analysis was performed.…”

Section: Methodsmentioning

confidence: 99%

Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy

et al. 2015

Self Cite

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BackgroundProstate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy.Material/MethodsWe evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR.ResultsThe ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy.ConclusionsPCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy.

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Promoter Methylation of Protocadherin8 is an Independent Prognostic Factor for Biochemical Recurrence of Early-Stage Prostate Cancer

Cited by 13 publications

References 27 publications

Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis

Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy

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