尿液基因检测在上尿路尿路上皮癌早期诊断中价值

Urine gene detection in the early diagnosis of upper tract urothelial carcinoma

目的 观察上尿路尿路上皮癌(upper tract urothelial carcinoma, UTUC)患者尿液尿路上皮肿瘤常见突变基因突变情况,探讨尿液基因检测对UTUC早期诊断的价值。方法 拟诊UTUC患者116例均行手术治疗,术前行尿脱落细胞学、荧光原位杂交检测,行尿液基因检测观察尿路上皮肿瘤常见突变基因突变及甲基化情况。以术后组织病理检查结果为金标准,比较尿脱落细胞学、荧光原位杂交、尿液基因检测诊断UTUC的灵敏度、特异度和准确率;绘制ROC曲线,评估尿脱落细胞学、荧光原位杂交、尿液基因检测术前诊断UTUC的效能。结果 基因测序结果显示,116例患者检出TP53基因突变32例,TERT基因突变44例,AKT1基因突变1例,ERBB2基因突变4例,ERCC2基因突变1例,FBXW7基因突变1例,FGFR3基因突变5例,HRAS基因突变10例,KRAS基因突变2例,PIK3CA基因突变10例,RHOA基因突变2例,SF3B1基因突变1例,U2AF1基因突变2例,ONECUT2 CpG位点甲基化62例。术后组织病理检查结果显示,UTUC 80例,非UTUC 36例。术前尿液基因检测诊断UTUC的灵敏度(92.50%)、准确率(93.10%)均高于尿脱落细胞学(37.50%、52.59%)、荧光原位杂交(45.00%、58.62%)(P<0.05),特异度(94.44%)与尿脱落细胞学(86.11%)、荧光原位杂交(88.89%)比较差异均无统计学意义(P>0.05)。术前尿脱落细胞学、荧光原位杂交、尿液基因检测诊断UTUC的AUC分别为0.618(95%CI:0.523~0.707,P=0.002)、0.673(95%CI:0.576~0.754,P<0.001)、0.935(95%CI:0.873~0.972,P<0.001),术前尿液基因检测诊断UTUC的AUC大于尿脱落细胞学、荧光原位杂交检测(Z=6.749,P<0.001;Z=5.767,P<0.001)。结论 尿液基因检测尿路上皮肿瘤常见突变基因突变及甲基化情况对UTUC的诊断价值较高。

Objective To observe the common gene mutations in urothelial carcinoma of patients with upper tract urothelial carcinoma(UTUC), and to explore the value of urine gene detection to the early diagnosis of UTUC. Methods Totally 116 patients with suspected UTUC were detected by urine exfoliative cytology and fluorescence in situ hybridization(FISH) before operation, and the mutation and methylation of common mutations in urothelial carcinoma were observed by urine gene detection. Taking the results of postoperative histopathological examination as the gold standard, the sensitivities, specificities and accuracies of urine exfoliative cytology, FISH and urine gene detection in the diagnosis of UTUC were compared, and the ROC curve was drawn to evaluate their efficacies on the diagnosis of UTUC before operation. Results The gene sequencing detected 32 cases of TP53 mutation, 44 cases of TERT mutation, 1 case of AKT1 mutation, 4 cases of ERBB2 mutation, 1 case of ERCC2 mutation, 1 case of FBXW7 mutation, 5 cases of FGFR3 mutation, 10 cases of HRAS mutation, 2 cases of KRAS mutation, 10 cases of PIK3 CA mutation, 2 cases of RHOA mutation, 1 case of SF3 B1 mutation, 2 cases of U2 AF1 mutation and 62 cases of ONECUT2 CpG site methylation. The postoperative histopathological examination showed 80 cases of UTUC and 36 cases of non-UTUC. The sensitivity and accuracy of preoperative urine gene detection(92.50%, 93.10%) in the diagnosis of UTUC were higher than those of urine exfoliative cytology(37.50%, 52.59%) and FISH(45.00%, 58.62%)(P<0.05), while the specificitiy showed no significant differences among them three(94.44%, 86.11%, 88.89%)(P>0.05). The AUC of urine gene detection [0.935(95%CI: 0.873-0.972, P<0.001)] was greater than that of urine exfoliative cytology [0.618(95%CI: 0.523-0.707, P=0.002)] and FISH [0.673(95%CI: 0.576-0.754, P<0.001)] for the diagnosis of UTUC before operation(Z=6.749, P<0.001;Z=5.767, P<0.001). Conclusion Urine gene detection of common mutations and methylation in urothelial carcinoma is of high value to the diagnosis of UTUC.