CAJ | 학술논문

目的探讨前列腺癌组织中RARβ2、GSTP1和DAPK基因异常甲基化,与前列腺临床病理特征间的关系,及其在前列腺癌诊断中价值.方法采用巢式甲基化特异性PCR(nestedmethylationspecificpolymerasechainreaction,NMSP)法对57例前列腺痛组织和35例良性前列腺增生(BPH)组织进行甲基化检测;分析其甲基化的发生与前列腺癌临床病理特征间的关系,以及在前列腺癌诊断中价值.结果前列腺癌组织中RARβ2、GSTPI和DAPK基因甲基化检出率显著高于BPH组织(RARβ32:52.6%对0%;GSTPl:61.4%对2.9%;DAPK:43.9%对8.6%;均P<0.01).RARβ2基因甲基化率在前列腺癌不同Gleason评分和不同临床分期之间差异有统计学意义(4～7分对8～10分:34.8%对64.7%,B、C期对D期:37.0%对66.7%,x2=4.927和x2=5.004,P=0.026和P=0.025);GSTP1基因甲基化率在不同Gleason评分间差异有统计学意义(4～7分对8～10分:43.5%对73.5%,x2=11.530,P=0.001),而在不同临床分期之间差异无统计学意义(B、C期对D期:51.9%对70.0%,x2=1.975,P=0.16);DAPK基因甲基化率在不同Gleason评分和不同临床分期之间差异均无统计学意义(4～7分对8～lO分:39.1%对50.0%,B、C期对D期:33.3%对53.3%,x2=1.290和x2=2.309,均P>0.05).GSTP1基因诊断敏感度最高为61.4%(35/57),特异度为97.1%(34/35);RARβ2基因特异度最高为100%(35/35),敏感度为52.6%(30/57);DAPK基因的诊断敏感度和特异度分别为43.9%和91.4%(25/57和32/35).而RARβ2、GSTP1和DAPK基因甲基化联合检测能明显提高前列腺癌诊断敏感度,但诊断特异度却有所下降.结论 RARβ2、GSTP1和DAPK基因异常甲基化与前列腺癌的发生与发展相关,可作为前列腺癌的诊断有效指标之一.
목적 탐토전렬선암조직중RARβ2、GSTP1화DAPK기인이상갑기화,여전렬선림상병리특정간적관계,급기재전렬선암진단중개치.방법 채용소식갑기화특이성PCR(nestedmethylationspecificpolymerasechainreaction,NMSP)법대57례전렬선통조직화35례량성전렬선증생(BPH)조직진행갑기화검측;분석기갑기화적발생여전렬선암림상병리특정간적관계,이급재전렬선암진단중개치.결과 전렬선암조직중RARβ2、GSTPI화DAPK기인갑기화검출솔현저고우BPH조직(RARβ32:52.6%대0%;GSTPl:61.4%대2.9%;DAPK:43.9%대8.6%;균P<0.01).RARβ2기인갑기화솔재전렬선암불동Gleason평분화불동림상분기지간차이유통계학의의(4～7분대8～10분:34.8%대64.7%,B、C기대D기:37.0%대66.7%,x2=4.927화x2=5.004,P=0.026화P=0.025);GSTP1기인갑기화솔재불동Gleason평분간차이유통계학의의(4～7분대8～10분:43.5%대73.5%,x2=11.530,P=0.001),이재불동림상분기지간차이무통계학의의(B、C기대D기:51.9%대70.0%,x2=1.975,P=0.16);DAPK기인갑기화솔재불동Gleason평분화불동림상분기지간차이균무통계학의의(4～7분대8～lO분:39.1%대50.0%,B、C기대D기:33.3%대53.3%,x2=1.290화x2=2.309,균P>0.05).GSTP1기인진단민감도최고위61.4%(35/57),특이도위97.1%(34/35);RARβ2기인특이도최고위100%(35/35),민감도위52.6%(30/57);DAPK기인적진단민감도화특이도분별위43.9%화91.4%(25/57화32/35).이RARβ2、GSTP1화DAPK기인갑기화연합검측능명현제고전렬선암진단민감도,단진단특이도각유소하강.결론 RARβ2、GSTP1화DAPK기인이상갑기화여전렬선암적발생여발전상관,가작위전렬선암적진단유효지표지일.
Objective To explore hypermethylation of RARβ2, GSTP1 and DAPK gene in prostate cancer tissues, and to explore its correlation with clinicopathological features of prostate cancer and its diagnostic value. Methods Hypermethylation of RARe2, GSTP1 and DAPK gene was detected by nested methylation-specific PCR (NMSP) in 57 prostate cancer (PCa) tissues and 35 benign prostate hyperplasia (BPH) tissues. The correlation between hypermethylation and clinicopathological features of prostate cancer and its diagnostic value were analyzed. Results The hypermethylation frequencies of RARβ2, GSTP1 and DAPK gene in PCa were significantly higher than those in BPH (RARβ2: 52.6% vs. 0% GSTP1: 61.4% vs. 2.9%;DAPK: 43.9% vs. 8.6%;all P<0.01). The methylation rate of RARβ2 gene was directly correlated with distinct Gleason scores and clinical stage (4～7 score vs. 8～10 score: 34.8% vs. 64.7%;stage B, C vs. stage D: 37.0% vs. 66.7%;x2=4.927 and 5.004, P=0.026 and 0.025). The methylation rate of GSTP1 gene was significantly different in patients with different Gleason scores (4～7 score vs. 8～10 score: 43.5% vs. 73.5%;x2 =11.530, P=0.001), but had no difference in patients with distinct clinical stage (stage B, C vs. stage D: 51.9% vs. 70.0%;x2=1.975, P=0.16) . There was no difference in DAPK gene methylation rate among patients with different Gleason scores and distinct clinical stage (4 ～7 score vs. 8～10 score: 39.1% vs. 50.0%;stage B, C vs. stage D: 33.3% vs. 53.3%;x2= 1.290 and 2.309, both P～0.05). GSTP1 gene showed the highest sensitivity of 61.4% (35/57)with specificity of 97.1%(34/35), while RARβ2 gene had the highest specificity of 100% (35/35) with the sensitivity of 52.6% (30/57). The sensitivity and specificity of DAPK gene were 43.9% and 91.4% (25/57 and 32/35), respeetively. When the hypermethylation of RARβ2, GSTP1 and DAPK gene were detected together, the diagnostic sensitivity was increased, but the specificity was decreased. Conclusions The aberrant methylation of RARβ2, GSTP1 and DAPK gene is correlated with tumorigenesis and progression of prostate cancer, which may be used as an effective diagnostic marker for prostate cancer.