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

Lin, Ying‐Li; Deng, Qiu-Kui; Wang, Yuhao; Fu, Xingli; Ma, Jun

doi:10.12659/msm.896763

Cited by 13 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar associations have also been reported in previous studies which suggested that RASSF1 , RARB2 , and/or GSTP1 ctDNA methylation may predict the stage and grade of localized PC (Sunami et al ., ). Furthermore, it has been proposed that GSTP1 , SRD5A2 , CYPIIAI , and PCDH17 ctDNA methylation may predict BCR risk after RP (Bastian et al ., ; Horning et al ., ; Lin et al ., ). Conceivably, the ctDNA methylation level in a liquid biopsy may therefore help assess PC aggressiveness at diagnosis.…”

Section: Discussionmentioning

confidence: 97%

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

et al. 2018

View full text Add to dashboard Cite

Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of specific genes has been suggested as novel candidate biomarkers for PC that may improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter methylation in prostate tissues, and ST6GALNAC3,ZNF660,CCDC181, and HAPLN3 promoter methylation in liquid biopsies. First, using four independent patient sample sets, including a total of 110 nonmalignant (NM) and 705 PC tissue samples, analyzed by methylation‐specific qPCR or methylation array, we found that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer‐specific with areas under the curve (AUC) of receiver operating characteristic (ROC) curve analysis of 0.917–0.995 and 0.846–0.903, respectively. Furthermore, ZNF660 hypermethylation was significantly associated with biochemical recurrence in two radical prostatectomy (RP) cohorts of 158 and 392 patients and remained significant also in the subsets of patients with Gleason score ≤7 (univariate Cox regression and log‐rank tests, P < 0.05), suggesting that ZNF660 methylation analysis can potentially help to stratify low‐/intermediate‐grade PCs into indolent vs. more aggressive subtypes. Notably, ZNF660 hypermethylation was also significantly associated with poor overall and PC‐specific survival in the RP cohort (n = 158) with long clinical follow‐up available. Moreover, as proof of principle, we successfully detected highly PC‐specific hypermethylated circulating tumor DNA (ctDNA) for ST6GALNAC3,ZNF660,HAPLN3, and CCDC181 in liquid biopsies (serum) from 27 patients with PC vs. 10 patients with BPH, using droplet digital methylation‐specific PCR analysis. Finally, we generated a three‐gene (ST6GALNAC3/CCDC181/HAPLN3) ctDNA hypermethylation model, which detected PC with 100% specificity and 67% sensitivity. In conclusion, we here for the first time demonstrate diagnostic biomarker potential of ST6GALNAC3 and ZNF660 methylation, as well as prognostic biomarker potential of ZNF660. Furthermore, we show that hypermethylation of four genes can be detected in ctDNA in liquid biopsies (serum) from patients with PC.

show abstract

Section: Discussionmentioning

confidence: 97%

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

“…The circulating DNA was extracted from 0.8 mL serum using the QIAmp DNA Blood Mini Kit (Qiagen, Valencia, CA, USA); the isolated DNA was modified with bisulfite using the EpiTect Bisulfite Kit (Qiagen, Valencia, CA, USA) according to the manufacturer’s instructions as described previously [ 17 , 22 ]. The methylation status of the PCDH17 in serum was detected using MSP, and the primers were used as previously reported [ 17 , 19 , 23 , 24 ]. Sequences for unmethylation were: forward 5′-AGATTATTGGGTGTTGTAGTTT-3′ and reverse 5′-AACCCTAACACAACATACACA-3′; and methylation: forward 5′-GATTATCGGGTGTCGTAGTTC-3′ and reverse 5′-CCCTAACGCAACGTACGCG-3′ [ 17 , 19 , 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

Lin

Wang

et al. 2017

Med Sci Monit

Self Cite

View full text Add to dashboard Cite

BackgroundCurrent studies indicated that PCDH17 functions as a tumor suppressor, which is frequently inactivated by aberrant promoter methylation in urologic tumors. The main purpose of this study was to investigate the methylation status of PCDH17 in serum and its clinical significance in renal cell carcinoma (RCC).Material/MethodsThe methylation status of PCDH17 in serum samples of 142 RCC patients and 34 controls was evaluated by methylation-specific PCR (MSP). Then we correlated PCDH17 methylation status with the clinicopathologic features of RCC patients and patient outcomes.ResultsWe found that PCDH17 was more frequently methylated in RCC patients than in controls. Moreover, PCDH17 methylation in serum was significantly correlated with advanced stage (p=0.044), higher grade (p=0.019), lymph node metastasis (p=0.008) and tumor progression (p<0.001). In addition, patients with methylated PCDH17 had shorter progression-free survival (p<0.001) and overall survival (p=0.017) than patients without, and PCDH17 methylation in serum was an independent prognostic factor for worse progression-free survival (HR: 4.215, 95% CI: 1.376–9.032, p<0.001) and overall survival (HR: 5.092, 95% CI: 1.149–12.357, p=0.046) of patients with RCC.ConclusionsThe present study indicates that PCDH17 methylation in serum is a frequent event in RCC and associated with risk factors of poor outcomes. Moreover, PCDH17 methylation in serum is a potential prognostic biomarker for patients with RCC after surgery.

show abstract

“…21,22 Recent studies showed that PCDH8, PCDH10 and PCDH17 acted as tumor suppressors in a variety of human cancers. [23][24][25][26][27][28][29][30][31][32][33][34] PCDH9 is another member of the PCDH family located in the 13q21.32 of human genome. Previous studies demonstrated that PCDH9 was down-regulated in cancers, such as glioblastoma, hepatocellular carcinoma and gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Shi¹,

Yang²,

Zhang³

et al. 2019

OTT

View full text Add to dashboard Cite

Background: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized. Materials and methods: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3ʹ-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis. Results: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3ʹ-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells. Conclusion: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.

show abstract

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

Cited by 13 publications

References 33 publications

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Contact Info

Product

Resources

About