尿液POU4F2基因甲基化对膀胱尿路上皮癌早期诊断的意义

Diagnosis of bladder cancer based on urinary levels of POU4F2 hypermethylation

目的寻找在中国人群中具有高敏感性、高特异性的膀胱癌甲基化标志物,以应用于膀胱癌的尿液诊断。方法先用T24细胞系筛选8种文献报道的膀胱癌甲基化标志物,再利用甲基化特异性荧光定量PCR(q MSP)技术分别在28例膀胱癌患者、10例尿路结石伴感染患者和30例健康志愿者尿液样品中检测筛选成功的4种甲基化标志物,计算出不同组合的敏感性和特异性。结果PCDH17、POU4F2、TCF21、ZNF154的敏感性分别为46.43%、92.86%、39.29%、46.43%,特异性分别为95.00%、97.50%、97.50%、100.00%,最优的诊断标志物为POU4F2(敏感性92.86%、特异性97.50%)。结论应用q MSP技术,以POU4F2为甲基化标志物在尿液中检测膀胱癌可能会成为一种临床可用的诊断方式。

Objective To identify a panel of novel epigenetic biomarkers with high sensitivity and specificity that can be utilized in detection and diagnosis of bladder cancer using urine sediments. Methods T24 cell lines that had been treated with bisulfite were used to examine the 8 methylated candidates that were previously reported in bladder cancer patients. Methylation levels of the candidate genes were quantified using the urine sediments from 28 bladder cancer patients, 30 healthy volunteers and 10 infected urinary calculi patients by quantitative methylation-specific polymerase chain reaction（qMSP）. The four most efficacious and reliable biomarkers were selected after the sensitivity and specificity of each biomarker were further calculated and inspected. Results The sensitivities of PCDH17, POU4F2, TCF21 and ZNF154 in the detection of bladder cancer were 46. 43%, 92. 86%, 39. 29% and 46. 43% respectively;the specificities of these biomarkers were 95. 00%, 97. 50%, 97. 50% and 100. 00% re-spectively. POU4F2 appeared as the best biomarkers among the four, showing a sensitivity of 92. 86% and a speci-ficity of 97 . 50%. Conclusion Bladder cancer can be detected by a biomarker panel by using qMSP depending on the urine samples from patients.