Aberrant Methylation of Protocadherin 17 and its Clinical Significance in Patients with Prostate Cancer after Radical Prostatectomy

Lin, Ying‐Li; Xie, Peigen; Wang, Lili; Ma, Jun

doi:10.12659/msm.891247

Cited by 24 publications

(19 citation statements)

References 35 publications

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“…The bisulfite conversion of DNA was carried out using EpiTect Bisulfite Kit (Qiagen, Valencia, CA) according to the manufacture’s protocol as reported previously [ 12 , 18 ]. Methylation analysis of bisulfite-treated DNA was carried out using PCR assay, and the primers specific for methylated PCDH17 and unmethylated PCDH17 were used as previously reported [ 14 , 22 ]. The primers for the methylated sequences were: 5′-GATTATCGGGTGTCGTAGTTC-3′ (forward) and 5′-CCCTAACGCAACGTACGCG-3′ (reverse).…”

Section: Methodsmentioning

confidence: 99%

“…The primers for the unmethylated sequences were: 5′-AGATTATTGGGTGTTGTAGTTT-3′ (forward) and 5′-AACCCTAACACAACATACACA-3′ (reverse). The PCR amplification was carried out as described previously [ 14 , 22 ]. In vitro methylated DNA and unmethylated DNA (New England Biolabs, Beverly, MA, USA) were used as methylation and unmethylation positive control.…”

Section: Methodsmentioning

confidence: 99%

“…The MSP products were separated in 2% agarose gel, stained with ethidium bromide, and visualized under ultraviolet illumination for analysis. The product was defined as methylation positive when methylated allele was present in the methylated DNA lane or both in the methylated and unmethylated DNA lanes, and methylation negative when band was present only in the unmethylated DNA lane [ 14 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies indicated that PCDH17 may function as a tumor suppressor gene in bladder cancer, prostate cancer, and gastric cancer. The PCDH17 gene is located on chromosome 13q21.2 in humans, and I often silenced by promoter methylation in some target CpG sites, such as −458, −731, and 870 in human cancers [ 13 – 16 ]. However, the clinical significance of PCDH17 methylation in ccRCC needs to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Protocadherin17 Promoter Methylation is a Potential Predictive Biomarker in Clear Cell Renal Cell Carcinoma

et al. 2015

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BackgroundProtocadherin17 (PCDH17) is a tumor suppressor gene, and is frequently silenced by promoter methylation in human cancers, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of PCDH17 methylation in ccRCC remains largely unclear. The aim of the present study was to investigate the methylation status of PCDH17 in ccRCC and its potential relevance to clinicopathological parameters and prognosis.Material/MethodsMethylation-specific PCR was used to examine the methylation status of PCDH17 in 191 ccRCC tumors and matched paired adjacent noncancerous tissues. Subsequently, the associations between PCDH17 methylation and clinicopathological parameters and prognosis of patients with ccRCC were analyzed.ResultsPCDH17 methylation occurred in 66.5% of ccRCC tumors, but in only 12.1% of adjacent noncancerous tissues. PCDH17 methylation is significantly correlated with advanced stage, higher grade, and lymph node metastasis in ccRCC. Moreover, it is an independent prognostic factor for progression-free survival and overall survival of patients with ccRCC.ConclusionsPCDH17 methylation occurred more frequently and was associated with malignant clinicopathological characteristics and poor prognosis in ccRCC patients. Thus, PCDH17 methylation may be used as a novel biomarker to predict the prognosis of patients with ccRCC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protocadherin17 Promoter Methylation is a Potential Predictive Biomarker in Clear Cell Renal Cell Carcinoma

et al. 2015

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“…Many studies on prostate carcinogenesis have focused on the role of genetic factors that mediate inflammatory response [ 9 – 12 ], as inflammation has been extensively linked to the etiology of prostate cancer, although other mechanisms such as cell adhesion also plays an important role [ 13 , 14 ]. Given the important role of inflammation in carcinogenesis, the present candidate gene association study focused on genes relevant to inflammation.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in NFKB1 and NFKBIA Genes Modulate the Risk of Developing Prostate Cancer among Han Chinese

et al. 2015

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BackgroundNuclear factor kappa B (NF-κB) pathway proteins play an important role in modulating inflammation and other carcinogenic processes. Polymorphisms within NF-κB pathway genes may influence cancer risk. This study aimed to examine the association between NFKB19-4 ATTG ins→del, NFKBIA 3′ UTR A→G, -826CT and -881AG polymorphisms and prostate cancer risk among Chinese.Material/MethodsThe polymorphisms were genotyped via PCR-RFLP technique on 936 prostate cancer patients and 936 population-based healthy controls. Logistic regression model was used to measure the risk association present.ResultsWith the exception of NFKBIA 3′ UTR polymorphism, the heterozygous and mutant genotypes of the other polymorphisms were significantly associated with prostate cancer risk. For NFKB1 polymorphism, a decreased risk was observed, with adjusted OR: 0.69; 95% CI: 0.44, 0.98; P=0.01 (heterozygous) and adjusted OR: 0.60; 95% CI: 0.37, 0.91; P=0.02 (mutant). NFKBIA -826CT and -881AG polymorphisms were in complete linkage disequilibrium and shared the same risk association, with adjusted OR: 1.34; 95% CI: 1.09, 1.62; P=0.02 (heterozygous) and adjusted OR: 2.83; 95% CI: 1.79, 4.50; P=0.01 (mutants). Interestingly, the impact of the NFKB1 polymorphism was not present in nonsmokers and younger (<60 years) subjects (P<0.05).ConclusionsIn conclusion, polymorphisms in NFKB1 and NFKBIA genes may modulate the risk of developing prostate cancer among Chinese.

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Recurrent transcriptional loss of the PCDH17 tumor suppressor in laryngeal squamous cell carcinoma is partially mediated by aberrant promoter DNA methylation

Byzia

Soloch

Bodnar

et al. 2018

Molecular Carcinogenesis

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Protocadherins are cell-cell adhesion molecules encoded by a large family of genes. Recent reports demonstrate recurrent silencing of protocadherin genes in tumors and provide strong arguments for their tumor supresor functionality. Loss of protocadherins may contribute to cancer development not only by altering cell-cell adhesion, that is a hallmark of cancer, but also by enhancing proliferation and epithelial mesenchymal transition of cells via deregulation of the WNT signaling pathway. In this study we have further corroborated our previous findings on the involvement of PCDH17 in laryngeal squamous cell carcinoma (LSCC). We used bisulfite pyrosequencing to analyze a cohort of primary LSCC tumors for alterations in PCDH17 promoter DNA methylation as an alternative gene inactivation mechanism to the homozygous deletions reported earlier. Moreover, we analyzed primary LSCC samples by immunohistochemistry for PCDH17 protein loss. We identified recurrent elevation of PCDH17 promoter DNA methylation in 32/81 (40%) primary tumors (P < 0.001) and therein hypermethylation of 12 (15%) cases in contrast to no tumor controls (n = 24) that were all unmethylated. Importantly, DNA demethylation by decitabine has restored low level PCDH17 expression in LSCC cell lines. In conclusion, we provide a mechanistic explanation of recurrently observed PCDH17 silencing in LSCC by demonstrating the role of promoter methylation in this process. In light of these findings and recent reports showing that PCDH17 methylation is detectable in serum of cancer patients we suggest that testing PCDH17 DNA methylation might serve as a potential biomarker in LSCC.

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Aberrant Methylation of Protocadherin 17 and its Clinical Significance in Patients with Prostate Cancer after Radical Prostatectomy

Cited by 24 publications

References 35 publications

Protocadherin17 Promoter Methylation is a Potential Predictive Biomarker in Clear Cell Renal Cell Carcinoma

Protocadherin17 Promoter Methylation is a Potential Predictive Biomarker in Clear Cell Renal Cell Carcinoma

Polymorphisms in NFKB1 and NFKBIA Genes Modulate the Risk of Developing Prostate Cancer among Han Chinese

Recurrent transcriptional loss of the PCDH17 tumor suppressor in laryngeal squamous cell carcinoma is partially mediated by aberrant promoter DNA methylation

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