一项新型基于尿液的utLIFE检测模型在UTUC早期诊断及术后监测中的价值研究  

Application of a novel urine DNA predictor for non-invasive early diagnosis and monitoring minimal residual disease in upper tract urothelial carcinoma

作　　者：左炜 郭璇骏 唐琦[1] 虞巍[1] 宋毅[1] 李学松[1] 周利群[1] 何志嵩[1] Zuo Wei;Guo Xuanjun;Tang Qi;Yu Wei;Song Yi;Li Xuesong;Zhou Liqun;He Zhisong(Department of Urology,Peking University First Hospital,Institute of Urology,Peking University,National Urological Cancer Center,Beijing 100034,China)

机构地区：[1]北京大学第一医院泌尿外科、北京大学泌尿外科研究所、国家泌尿男生殖系肿瘤研究中心,北京100034

出　　处：《中华泌尿外科杂志》2023年第9期661-664,共4页Chinese Journal of Urology

基　　金：中央高水平医院临床科研业务费资助(2022CR96)。

摘　　要：目的探讨基于尿液的多维生物信息学评价模型(utLIFE模型)在上尿路尿路上皮癌(UTUC)早期诊断及术后监测中的价值。方法收集北京大学第一医院2022年8月至2022年10月术前临床诊断为UTUC且不合并膀胱癌患者的晨尿标本。留取手术当日术前及术后出院日的尿液标本,提取DNA,进行基因测序。利用本中心既往在膀胱癌队列中构建的utLIFE模型,基于155个基因突变位点和拷贝数变异水平计算模型评分,评分≥60分为utLIFE阳性。以术后病理作为诊断的金标准,分析utLIFE模型诊断UTUC的敏感性。并比较术前术后的utLIFE评分。结果本研究共纳入53例患者,术后病理均确诊为UTUC。53例中位年龄66(59,72)岁。24例(45.3%)肿瘤位于肾盂,26例(49.1%)位于输尿管,2例(5.7%)同时累及肾盂和输尿管。T_(1)期27例(50.9%),≥T_(2)期26例(49.1%)。53例术前utLIFE评分为79(70,84)分。术前utLIFE诊断UTUC的敏感性为96.2%(51/53)。utLIFE模型在T_(1)期和≥T_(2)期中显示出相似的敏感性[100.0%(27/27)与92.3%(24/26),P=0.236],在N_(0)期和≥N_(1)期也显示出相似的敏感性[95.0%(38/40)与100.0%(5/5),P=1.000]。此外,术前utLIFE检测UTUC的敏感性高于尿细胞学检查[95.2%(20/21)与23.8%(5/21),P<0.001]、荧光原位杂交(FISH)[92.6%(25/27)与55.5%(15/27),P=0.004]和输尿管镜检查[86.7%(13/15)与60.0%(9/15),P=1.000]。术后收集到45例标本,术后utLIFE评分明显低于术前[36(18,61)分与79(70,84)分,P<0.001]。结论utLIFE作为一种无创尿液DNA生物信息学评估模型,在UTUC早期诊断方面敏感性高,显著优于细胞学检查和FISH,并可用于监测围手术期微小残留病的水平。Objective To study the value of urine-based multi-dimensional bioinformatics evaluation model(utLIFE model)in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma(UTUC).Methods Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected.Urine samples were collected before and after surgery,and DNA was extracted for gene sequencing.The utLIFE model previously constructed by our center was used to calculate the score,based on 155 gene mutation sites and copy number variation,and the score≥60 was defined as utLIFE positive.The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard.The utLIFE scores before and after operation were also compared.Results A total of 53 patients were included in this study,all of whom were confirmed as UTUC by postoperative pathology.The median age of patients was 66(59,72)years.Twenty-four cases(45.3%)of UTUC tumors were located in the renal pelvis,26 cases(49.1%)were located in the ureter,and 2 cases(5.7%)involved both ureter and renal pelvis.There were 27 patients(50.9%)at T_(1)stage and 26 patients(49.1%)at≥T_(2)stage.Preoperative utLIFE score of 53 patients was 79(70,84).The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2%(51/53).utLIFE showed similar high sensitivity in T_(1)stage and≥T_(2)stage[100.0%(27/27)vs.92.3%(24/26),P=0.236],in N_(0)and≥N_(1)stage[95.0%(38/40)vs.100.0%(5/5),P=1.000].In addition,the sensitivity of preoperative utLIFE was higher than that of urine cytology[95.2%(20/21)vs.23.8%(5/21).P<0.001],fluorescence in situ hybridization(FISH)[92.6%(25/27)vs.55.5%(15/27),P=0.004]and ureteroscopy[86.7%(13/15)vs.60.0%(9/15),P=1.000].A total of 45 patients postoperative utLIFE samples were collected,and the postoperative utLIFE score was significantly lower than that of preoperative[36(18,61)vs.79(70,84),P<0.001].Conclusions utLIFE,as a non-invasive

关 键 词：上尿路尿路上皮癌 尿液肿瘤DNA 液体活检 早期诊断 

分 类 号：R737.1[医药卫生—肿瘤]