Inactivation of RASSF1A, RARβ2 and DAP-kinase by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Fendri, Ali; Masmoudi, Asma; Khabir, Abdelmajid; Sellami‐Boudawara, Tahya; Daoud, J.; Frikha, M.; Ghorbel, Abdelmonem; Gargouri, Ali; Mokdad-Gargouri, Raja

doi:10.4161/cbt.8.5.7686

Cited by 49 publications

(59 citation statements)

References 26 publications

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“…Evidence has demonstrated that human papillomavirus (HPV) infection is a key pathogenic factor in cervical cancer and precancerous lesions. However, the HPV infection in the majority of patients may resolve spontaneously, and only a minority of patients positive for HPV develop cervical cancer (1). The findings suggest the HPV infection is not the unique cause of cervical cancer.…”

Section: Introductionmentioning

confidence: 96%

Expressions of sFRP1 and β-Catenin in Cervical Cancer

Zhang¹,

Wang²,

Qiao³

et al. 2012

Journal of Medical Biochemistry

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Summary: This study aimed to investigate the expressions of secreted frizzled-related protein 1 (sFRP1) and b-catenin in cer vical cancer and cervical intraepithelial neoplasia (CIN), and to explore the relationship between both proteins and the prognosis of cervical cancer. Immunohistochemistry was performed to detect the protein expressions of sFRP1 and b-catenin in cervical cancer (n=78), CIN (n=30) and normal cervical tissues (n=20), and the relationships of sFRP1 and b-catenin with the clinicopathological charac teris tics and prognosis of cervical cancer were analyzed. The positive rate of sFRP1 was 100%, 70% and 33.3% in the normal cervical tissues, CIN and cervical cancer, respectively (P<0.05). The sFRP1 expression was positively correlated with the stage of cervical cancer and lymphatic metastasis (P<0.05). The 5-year survival rate was significantly higher in patients positive for sFRP1 than in those negative for sFRP1 (P<0.05). The rate of abnormal b-catenin expression in the normal cervical tissues, CIN and cervical cancer was 5%, 43.3% and 70.5%, respectively (P<0.05). The ab nor mal b-catenin expres sion was positively correlated with the stage of cervical cancer, lymphatic metastasis and patho lo gical grade (P<0.05). The 5-year survival rate was markedly higher in patients with normal b-catenin expression than in those with abnormal b-catenin expression (P<0.05). The sFRP1 expression was negatively related to the b-catenin expression in cervical cancer (r = -0.557, P<0.001). Both sFRP1 and b-catenin play important roles in the initiation and development of cervical cancer, and both proteins can be used as indicators predicting the prognosis of cervical cancer.Keywords: cervical cancer, secreted frizzled-related protein 1, b-catenin, immunohistochemistry, prognosis Kratak sadr`aj: U ovoj studiji ispitivana je ekspresija sFRP1 i b-katenina u karcinomu grli}a materice i cervikalnoj intraepitelnoj neoplaziji (CIN), kao i odnos izme|u ova dva proteina i prognoze u karcinomu grli}a materice. Imuno histohemijskim putem utvr|ena je ekspresija proteina sFRP1 i b-katenina u karcinomu grli}a materice (n=78), CIN (n=30) i zdravom cervikalnom tkivu (n=20). Analizirana je pove zanost sFRP1 i b-katenina sa klini~ko-patolo{kim karakteristikama i prognozom u karcinomu grli}a materice. Pozitivna stopa sFRP1 bila je 100%, 70% i 33,3% u zdravim cervikalnim tkivima, CIN i karcinomu grli}a materice (p<0,05). Ekspresija sFRP1 pozitivno je korelisala sa stadijumom karcinoma grli}a materice i limfnim metastazama (p<0,05). Stopa petogodi{njeg pre`ivljavanja bila je zna~ajno vi{a kod pacijenata pozitivnih na sFRP1 nego kod onih kod kojih je sFRP1 bio negativan (p<0,05). Stopa abnormalne ekspresije b-katenina u zdravim cervikalnim tkivima, CIN i karcinomu grli}a materice bila je 5%, 43,3% i 70,5% (p<0,05). Abnormalna ekspresija b-katenina bila je u pozitivnoj korelaciji sa stadijumom karcinoma grli}a materice, limfnim metastazama i patolo{kim stepenom (p<0,05). Stopa petogodi{ njeg pre`ivljavanja bila je izrazito vi{a kod p...

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Section: Introductionmentioning

confidence: 96%

Expressions of sFRP1 and β-Catenin in Cervical Cancer

Zhang¹,

Wang²,

Qiao³

et al. 2012

Journal of Medical Biochemistry

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“…After being selected in accordance with the inclusive criteria, our final eligible studies included 14 studies, as shown in Figure 1 (Lo et al, 2001;Kwong et al, 2002;Tong et al, 2002;Chang et al, 2003;Wong et al, 2003;Qiu et al, 2004;Wong et al, 2004;Zhou et al, 2005;Tan et al, 2006;Fendri et al, 2009;Challouf et al, 2012;Yang et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…Hypermethylation of tumor suppressor genes (TSGs) has been found in most human cancers (Baylin, 2005;Hesson et al, 2007). The gene Ras association domain family 1A (RASSF1A) has been widely studied as a methylation biomarker and a TSG in NPC since its discovery in lung cancer in 2000 (Dammann et al, 2000;Lo et al, 2001 However, even if lots of studies have been evaluated the association between promoter methylation of RASSF1A gene and the risk of NPC (Fendri et al, 2009;Challouf et al, 2012;Yang et al, 2014), the results from those studies remain conflicting rather than conclusive. Thus, we carried out a meta-analysis based on all eligible casecontrol literature to assess the association of RASSF1A gene promoter methylation with the risk of NPC.…”

Section: Introductionmentioning

confidence: 99%

RASSF1A Gene Methylation is Associated with Nasopharyngeal Carcinoma Risk in Chinese

Xu²,

Chen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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In order to explore the association between RASSF1A methylation and nasopharyngeal carcinoma (NPC) risk of Chinese, we carried out a meta-analysis with searches of PubMed, Web of Science, ProQest and Medline databases. Ultimately, 14 articles were identified and analysised using R Software (R version 3.1.2) including meta packages. Overall, we found a significant relationship between RASSF1A methylation and NPC risk (OR 30.7; 95 % CI, 16.71~56.23; z=11.0591; p<0.0001) in a fixed effects model and (OR 32.1; 95% CI, 14.27~72.01; z=8.3984; p<0.0001) in a random effects model pooled. In tissue and NP brushings groups , similar results were found. Hence, our study identified a strong association between RASSF1A methylation and NPC and highlighted a promising potential for RASSF1A methylation in NPC risk prediction of Chinese.

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“…A recent study demonstrated the prognostic significance of PTGS2 (COX2) mRNA expression, suggesting that mRNA overexpression of the PTGS2 gene may be useful for identifying NPC patients with lymph node metastasis (28). Additionally, it has been shown that aberrant promoter methylation of RASSF1, RARB and DAPK1 is an important indicator of advanced tumor stage and lymph node metastasis in NPC (29). Recently, cytoplasmic heterogeneous nuclear ribonucleoprotein K (HNRNPK) and thymidine phosphorylase (TYMP) have been proposed as independent prognostic and therapeutic markers for NPC (30).…”

Section: Discussionmentioning

confidence: 99%

BCL2L12 is a Novel Biomarker for the Prediction of Short-Term Relapse in Nasopharyngeal Carcinoma

Fendri

Kontos

Khabir

et al. 2010

Mol Med

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BCL2-like 12 (BCL2L12 ) is a new member of the apoptosis-related BCL2 gene family, members of which are implicated in various malignancies. Nasopharyngeal carcinoma is a highly metastatic, malignant epithelial tumor, with a high prevalence in Southeast Asia and North Africa. The purpose of the current study was to quantify and investigate the expression levels of the BCL2L12 gene in nasopharyngeal carcinoma biopsies and to assess its prognostic value. Total RNA was isolated from 89 malignant and hyperplastic nasopharyngeal biopsies from Tunisian patients. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. A highly sensitive real-time polymerase chain reaction (PCR) method for BCL2L12 mRNA quantification was developed using SYBR ® Green chemistry. GAPDH served as a reference gene. Relative quantification analysis was performed using the comparative C T (2 -ΔΔCT ) method. Higher BCL2L12 mRNA levels were detected in undifferentiated carcinomas of the nasopharynx, rather than in nonkeratinizing nasopharyngeal tumors (P = 0.045). BCL2L12 expression status was also found to be positively associated with the presence of distant metastases (P = 0.014). Kaplan-Meier survival analysis demonstrated that patients with BCL2L12-positive nasopharyngeal tumors have significantly shorter disease-free survival (P = 0.020). Cox regression analysis showed BCL2L12 expression to be an unfavorable and independent prognostic indicator of short-term relapse in nasopharyngeal carcinoma (P = 0.042). Our results suggest that mRNA expression of BCL2L12 may constitute a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma.

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Inactivation of RASSF1A, RARβ2 and DAP-kinase by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Cited by 49 publications

References 26 publications

Expressions of sFRP1 and β-Catenin in Cervical Cancer

Expressions of sFRP1 and β-Catenin in Cervical Cancer

RASSF1A Gene Methylation is Associated with Nasopharyngeal Carcinoma Risk in Chinese

BCL2L12 is a Novel Biomarker for the Prediction of Short-Term Relapse in Nasopharyngeal Carcinoma

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