Han Jang Hee, Jeong Seung-Hwan, Kim Si Hyun, Yuk Hyeong Dong, Jeong Chang Wook, Kwak Cheol, Ku Ja Hyeon
Department of Urology, Seoul National University Hospital, Seoul, South Korea.
Department of Urology, Seoul National University College of Medicine, Seoul, South Korea.
Front Oncol. 2022 Oct 11;12:1008763. doi: 10.3389/fonc.2022.1008763. eCollection 2022.
Kidney tubular damage markers are biomarkers of acute or chronic kidney injury. Hypothetically, upper tract urothelial cancer (UTUC), which induces obstructive uropathy or direct invasion of the renal parenchyma, may also induce increased excretion of urinary tubular damage proteins. Therefore, this study aimed to investigate the use of tubular damage biomarker as prognostic markers for UTUC.
The records of 417 surgically resected patients with UTUC were obtained from the Seoul National University Prospectively Enrolled Registry for urothelial cancer-upper tract urothelial cancer (SUPER-UC-UTUC) between January 2016 and December 2020. Patients with non-urothelial cancer or without urinary tubular injury marker measurement were excluded, and finally, 296 patients were finally included. B2-microglobulin (B2-MG) was an injury marker, and a value higher than 0.3 was considered abnormally elevated, according to previous studies.
The mean age was 70.9 years, and the male sex was predominant (n = 211, 71.3%). The incidences of renal pelvis and ureter cancer were similar (50.7% vs. 49.3%). Most patients had high-grade diseases (n = 254, 88.8%). The high urine B2-MG group was older, had decreased renal function, and had a higher pathologic T stage than did the low group. Multivariate Cox regression analysis of disease-free survival (DFS), open surgical method (Hazard ratio (HR) 1.52, p = 0.027), large tumor size (HR 1.06, p = 0.017), tumor multifocality (HR 1.90, p = 0.038), lymphovascular invasion (HR 2.19, p < 0.001), and high urine B2-MG (HR 1.57, p = 0.021) were significantly associated with shortened metastasis-free survival (MFS). Kaplan-Meier curve analysis revealed short DFS (median survival 15.5 months vs. unattained, log-rank p = 0.001) and MFS (unattained median survival in both groups, log-rank p = 0.003) for the high urine B2-MG group compared to the low urine B2-MG group.
Patients with UTUC presenting with increased pre-operative urine B2-MG levels were associated with disease recurrence and metastasis. This biomarker may aid in performing pre-operative risk stratification and in assessing the individual prognosis of patients with UTUC.
肾小管损伤标志物是急性或慢性肾损伤的生物标志物。据推测,上尿路尿路上皮癌(UTUC)可导致梗阻性尿路病或直接侵犯肾实质,也可能导致肾小管损伤蛋白的尿排泄增加。因此,本研究旨在探讨使用肾小管损伤生物标志物作为UTUC的预后标志物。
2016年1月至2020年12月期间,从首尔国立大学前瞻性登记的尿路上皮癌-上尿路尿路上皮癌(SUPER-UC-UTUC)中获取417例接受手术切除的UTUC患者的记录。排除非尿路上皮癌患者或未测量肾小管损伤标志物的患者,最终纳入296例患者。根据先前的研究,β2-微球蛋白(B2-MG)是一种损伤标志物,高于0.3的值被认为异常升高。
平均年龄为70.9岁,男性占主导(n = 211,71.3%)。肾盂癌和输尿管癌的发病率相似(50.7%对49.3%)。大多数患者患有高级别疾病(n = 254,88.8%)。高尿B2-MG组患者年龄更大,肾功能下降,病理T分期高于低B2-MG组。无病生存期(DFS)的多因素Cox回归分析显示,开放手术方式(风险比(HR)1.52,p = 0.027)、肿瘤体积大(HR 1.06,p = 0.017)、肿瘤多灶性(HR 1.90,p = 0.038)、淋巴管侵犯(HR 2.19,p < 0.001)和高尿B2-MG(HR 1.57,p = 0.021)与无转移生存期(MFS)缩短显著相关。Kaplan-Meier曲线分析显示,与低尿B2-MG组相比,高尿B2-MG组的DFS较短(中位生存期15.5个月对未达到,对数秩检验p = 0.001),MFS也较短(两组中位生存期均未达到,对数秩检验p = 0.003)。
术前尿B2-MG水平升高的UTUC患者与疾病复发和转移相关。该生物标志物可能有助于进行术前风险分层并评估UTUC患者的个体预后。