Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eur Urol Oncol. 2018 Oct;1(5):364-377. doi: 10.1016/j.euo.2018.04.015. Epub 2018 Jun 13.
Plasma glycosaminoglycan (GAG) measurements, when aggregated into diagnostic scores, accurately distinguish metastatic clear-cell renal cell carcinoma (RCC) from healthy samples and correlate with prognosis. However, it is unknown if GAG scores can detect RCC in earlier stages or if they correlate with prognosis after surgery.
To explore the sensitivity and specificity of plasma GAGs for detection of early-stage RCC and prediction of recurrence and death after RCC surgery.
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case-control study consisting of a consecutive series of 175 RCC patients surgically treated between May 2011 and February 2014 and 19 healthy controls.
Plasma GAGs in preoperative and postoperative RCC and healthy samples were measured using capillary electrophoresis with laser-induced fluorescence in a single blinded laboratory. A discovery set was first analyzed to update the historical GAG score. The sensitivity of the new GAG score for RCC detection versus healthy subjects was validated using the remaining samples. The correlation of the new GAG score to histopathologic variables, overall survival, and recurrence-free survival was evaluated using nonparametric and log-rank tests and multivariable Cox regression analyses.
The RCC cohort included 94 stage I, 58 stage II-III, and 22 stage IV cases. In the first discovery set (n=67), the new GAG score distinguished RCC from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.999. In the validation set (n=108), the GAG score achieved an AUC of 0.991, with 93.5% sensitivity. GAG scores were elevated in RCC compared to healthy samples, irrespective of and uncorrelated to stage, grade, histology, age, or gender. The total chondroitin sulfate concentration was an independent prognostic factor for both overall and recurrence-free survival (hazard ratios 1.51 and 1.25) with high concordance when combined with variables available at pathologic diagnosis (C-index 0.926 and 0.849) or preoperatively (C-index 0.846 and 0.736). Limitations of the study include its retrospective nature and moderate variability in GAG laboratory measurements.
Plasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC independent of stage, grade, or histology. Prospective validation studies on GAG scores for early detection, prediction, and surveillance for RCC recurrence are thus warranted.
In this study, we examined if a new molecular blood test can detect renal cell carcinoma in the early stages and predict if the cancer might relapse after surgery. The trial is registered on ClinicalTrial.gov as NCT03471897.
血浆糖胺聚糖（GAG）测量值聚合为诊断评分，可以准确区分转移性透明细胞肾细胞癌（RCC）与健康样本，并与预后相关。然而，目前尚不清楚 GAG 评分是否可以检测到早期 RCC，或者它们是否与手术后的预后相关。
探讨血浆 GAG 检测早期 RCC 以及预测 RCC 手术后复发和死亡的敏感性和特异性。
设计、地点和参与者：这是一项回顾性病例对照研究，包括 2011 年 5 月至 2014 年 2 月期间接受手术治疗的 175 例 RCC 患者和 19 名健康对照者的连续系列。
采用毛细管电泳激光诱导荧光法在单盲实验室中测量术前和术后 RCC 及健康样本中的血浆 GAG。首先分析发现集以更新历史 GAG 评分。使用其余样本验证新 GAG 评分对 RCC 检测与健康受试者的敏感性。使用非参数和对数秩检验以及多变量 Cox 回归分析评估新 GAG 评分与组织病理学变量、总生存和无复发生存的相关性。
RCC 队列包括 94 例 I 期、58 例 II-III 期和 22 例 IV 期病例。在第一个发现集（n=67）中，新的 GAG 评分在 RCC 与健康样本之间的受试者工作特征曲线（AUC）下面积为 0.999。在验证集（n=108）中，GAG 评分的 AUC 为 0.991，灵敏度为 93.5%。GAG 评分在 RCC 中高于健康样本，与分期、分级、组织学、年龄或性别无关且不相关。硫酸软骨素总量是总生存和无复发生存的独立预后因素（危险比分别为 1.51 和 1.25），与病理诊断时可用的变量（C 指数 0.926 和 0.849）或术前（C 指数 0.846 和 0.736）联合具有高度一致性。研究的局限性包括其回顾性性质和 GAG 实验室测量的中等变异性。
在接受手术治疗的 RCC 中，血浆 GAG 是高度敏感的诊断和预后生物标志物，与分期、分级或组织学无关。因此，有必要对 GAG 评分进行早期检测、预测和监测 RCC 复发的前瞻性验证研究。
在这项研究中，我们研究了一种新的分子血液检测方法是否可以在早期阶段检测肾细胞癌，并预测癌症在手术后是否会复发。该试验在 ClinicalTrials.gov 上注册为 NCT03471897。
