口腔鳞状细胞癌组织PRSS8基因启动子甲基化状态及其临床意义
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摘要
目的本实验通过分析口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)组织、癌旁组织中PRSS8基因启动子甲基化状态及其mRNA的表达情况,初步探索口腔鳞癌的发生、发展机制。方法应用甲基化特异性聚合酶链反应(Methylation Specific PCR,MSP)检测52例(河北医科大学第四医院)经术后病理诊断为OSCC的癌组织及癌旁组织中PRSS8基因启动子区甲基化状态,分析其与临床病理分期的关系。应用逆转录-聚合酶链反应(Reverse Transcriptase-PCR,RT-PCR)技术检测OSCC组织及癌旁组织中PRSS8的mRNA相对表达情况,分析其与临床病理分期的关系。结果 OSCC组织PRSS8基因启动子甲基化率均明显高于癌旁组织,(57.7%vs 34.6%χ~2=5.571,P=0.018),PRSS8基因甲基化状态与分化程度、淋巴结转移、病理分级相关(P<0.05),OSCC组织中PRSS8mRNA的表达水平明显低于癌旁组织,差异具有统计学意义(t=-10.620, P=0.000),OSCC组织中PRSS8基因mRNA的表达与分化程度、淋巴结转移、病理分级相关(P<0.05)。结论 PRSS8基因启动子区高甲基化可能与口腔鳞癌的发生及进展相关,有可能成为口腔鳞癌预后的重要指标。
Objective To investigate the methylation status of PRSS8 gene promoter and its mRNA expression in oral squamous cell carcinoma(OSCC) tissues and adjacent tissues, and to explore the mechanism of occurrence and development of oral squamous cell carcinoma. Methods Methylation-specific polymerase chain reaction(MSP) was used to detect the promoter region of PRSS8 gene in 52 cases of cancer tissues and adjacent tissues after pathological diagnosis of OSCC in the Fourth Hospital of Hebei Medical University. Methylation status, analysis of its relationship with clinical pathological staging. Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the relative expression of PRSS8 mRNA in OSCC tissues and paracancerous tissues, and its relationship with clinical pathological staging was analyzed. Results The methylation rate of PRSS8 gene promoter in OSCC tissues was significantly higher than that in adjacent tissues(57.7% vs 34.6% χ~2=5.571, P=0.018). The methylation status and differentiation degree of PRSS8 gene, lymph node metastasis and pathological grading Correlation(P <0.05), the expression level of PRSS8 mRNA in OSCC tissues was significantly lower than that in adjacent tissues, the difference was statistically significant(t=-10.620, P=0.000). The expression and differentiation of PRSS8 mRNA in OSCC tissues, lymph nodes Metastasis and pathological grading were associated(P <0.05). Conclusion Hypermethylation of the promoter region of PRSS8 gene may be associated with the occurrence and progression of oral squamous cell carcinoma, and may be an important indicator of prognosis of oral squamous cell carcinoma.
Objective To investigate the methylation status of PRSS8 gene promoter and its mRNA expression in oral squamous cell carcinoma(OSCC) tissues and adjacent tissues, and to explore the mechanism of occurrence and development of oral squamous cell carcinoma. Methods Methylation-specific polymerase chain reaction(MSP) was used to detect the promoter region of PRSS8 gene in 52 cases of cancer tissues and adjacent tissues after pathological diagnosis of OSCC in the Fourth Hospital of Hebei Medical University. Methylation status, analysis of its relationship with clinical pathological staging. Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the relative expression of PRSS8 mRNA in OSCC tissues and paracancerous tissues, and its relationship with clinical pathological staging was analyzed. Results The methylation rate of PRSS8 gene promoter in OSCC tissues was significantly higher than that in adjacent tissues(57.7% vs 34.6% χ~2=5.571, P=0.018). The methylation status and differentiation degree of PRSS8 gene, lymph node metastasis and pathological grading Correlation(P <0.05), the expression level of PRSS8 mRNA in OSCC tissues was significantly lower than that in adjacent tissues, the difference was statistically significant(t=-10.620, P=0.000). The expression and differentiation of PRSS8 mRNA in OSCC tissues, lymph nodes Metastasis and pathological grading were associated(P <0.05). Conclusion Hypermethylation of the promoter region of PRSS8 gene may be associated with the occurrence and progression of oral squamous cell carcinoma, and may be an important indicator of prognosis of oral squamous cell carcinoma.
引文
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16 Gurkiran Kaur,Sunitha Carnelio,Nirmala Rao,et al.Expression of ecadherin in primary oral squamous cell carcinoma and metastatic lymph nodes:An immunohistochemical study.Indian J Dent Res,2009,20(1):71-76.
17 Lai Ping Zhong,Jiang Li,Chen Ping Zhang,et al.Expression of Ecadherin in cervical lymph nodes from primary oral squamous cell carcinoma patients.Arch Oral Biol,2007,52(8):740-747.
18 Diniz-Freitas M,Garcia-Caballero T,Antunez-Lopez J,et al.Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma.Oral Oncol,2006,42:190-200.
2 Uchimura K,Hayata M,Mizumoto T,et al.The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling.Nat Commun,2014,5:3428.DOI:10.1038/ncomms4428.
3 Sakashita K,Mimori K,Tanaka F,et al.Clinical significance of low expression of Prostasiu m RNA in human gastric tauter.JSurg Oncol,2008,98(7):559-564.
4 Chen LM,KX Chai,et al.Prostasiu seriue protease inhibits breast tauter iuvasiveuess and is trauscriptioually regulated promoter methylation.Int J Cancer,2002,97(3):323-329.
5 Bao Y,et al.PRSS8 methylation and its significance in esophageal squamous cell carcinoma.Oncotarget,2016,7(19):28540-28555.
6 Chen LM,NJ Verity,KX Chai.Loss of prostasin(PRSSB)in human bladder transitional carcinoma cell lines is associated with epithelial-mesenchymal transition(EMT).BMC Cancer,2009,9:377.
7 Chen LM,X Zhang,KX Chai.Regulation of prostasin expression and function in the prostate.Prostate,2004,59(1):1-12.9.
8 Takahashi S,et al.Down-regulated expression of prostasin in high-grade or hormone-refractory human prostate cancers.Prostate,2003,54(3):187-193.
9 KF Hung,CS Chang,CJ Liu,et al.Differential expression of E-cadherin in metastatic lesions comparing to primary oral squamous cell carcinoma.J Oral Pathol Med,2006,35:589-594.
10 Barr S,Thomson S,Buck E,et al.Bypassing cellular EGFreceptor dependence through epithelial-to-mesenchymal-like transitions.Clin Exp Metastasis,2008,25:685-693.
11 Baranwal S,SK Alahari,et al.Molecular mechanisms controlling E-cadheriu expression in breast cancer.Biochem Biophys Res Commun,2009,384(1):6-11.
12 Yang CC,DA Wolf.Inflamed snail speeds metastasis.Cancer Cell,2009,15(5):355-357.
13 Yang J,RA Weinberg.Epithelial-meseuchymal transition:at the crossroads of development and tumor metastasis.Dev Cell,2008,14(6):818-829.
14 Onder TT,et al.Loss of E-cadheriu promotes metastasis via multiple downstream trauscriptioual pathways.Cancer Res,2008,68(10):3645-3654.
15 Gurkiran Kaur,Sunitha Carnelio,Nirmala Rao,et al.Expression of Ecadherin in primary oral squamous cell carcinoma and metastatic lymph nodes:An immunohistochemical study.Indian J Dent Res,2009,20(1):71-76.
16 Gurkiran Kaur,Sunitha Carnelio,Nirmala Rao,et al.Expression of ecadherin in primary oral squamous cell carcinoma and metastatic lymph nodes:An immunohistochemical study.Indian J Dent Res,2009,20(1):71-76.
17 Lai Ping Zhong,Jiang Li,Chen Ping Zhang,et al.Expression of Ecadherin in cervical lymph nodes from primary oral squamous cell carcinoma patients.Arch Oral Biol,2007,52(8):740-747.
18 Diniz-Freitas M,Garcia-Caballero T,Antunez-Lopez J,et al.Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma.Oral Oncol,2006,42:190-200.