Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
JCO Precis Oncol. 2023 Feb;7:e2200361. doi: 10.1200/PO.22.00361.
No liquid biomarkers are approved in metastatic renal cell carcinoma (mRCC) despite the need to predict and monitor response noninvasively to tailor treatment choices. Urine and plasma free glycosaminoglycan profiles (GAGomes) are promising metabolic biomarkers in mRCC. The objective of this study was to explore if GAGomes could predict and monitor response in mRCC.
We enrolled a single-center prospective cohort of patients with mRCC elected for first-line therapy (ClinicalTrials.gov identifier: NCT02732665) plus three retrospective cohorts (ClinicalTrials.gov identifiers: NCT00715442 and NCT00126594) for external validation. Response was dichotomized as progressive disease (PD) versus non-PD every 8-12 weeks. GAGomes were measured at treatment start, after 6-8 weeks, and every third month in a blinded laboratory. We correlated GAGomes with response and developed scores to classify PD versus non-PD, which were used to predict response at treatment start or after 6-8 weeks.
Fifty patients with mRCC were prospectively included, and all received tyrosine kinase inhibitors (TKIs). PD correlated with alterations in 40% of GAGome features. We developed plasma, urine, and combined glycosaminoglycan progression scores that monitored PD at each response evaluation visit with the area under the receiving operating characteristic curve (AUC) of 0.93, 0.97, and 0.98, respectively. For internal validation, the scores predicted PD at treatment start with the AUC of 0.66, 0.68, and 0.74 and after 6-8 weeks with the AUC of 0.76, 0.66, and 0.75. For external validation, 70 patients with mRCC were retrospectively included and all received TKI-containing regimens. The plasma score predicted PD at treatment start with the AUC of 0.90 and at 6-8 weeks with the AUC of 0.89. The pooled sensitivity and specificity were 58% and 79% at treatment start. Limitations include the exploratory study design.
GAGomes changed in association with mRCC response to TKIs and may provide biologic insights into mRCC mechanisms of response.
尽管需要非侵入性地预测和监测反应以定制治疗选择，但转移性肾细胞癌 (mRCC) 仍没有批准的液体生物标志物。尿液和血浆游离糖胺聚糖谱 (GAGome) 是 mRCC 有前途的代谢生物标志物。本研究的目的是探讨 GAGome 是否可以预测和监测 mRCC 的反应。
我们招募了一个单中心前瞻性队列的 mRCC 患者，他们选择一线治疗（ClinicalTrials.gov 标识符：NCT02732665），外加三个回顾性队列（ClinicalTrials.gov 标识符：NCT00715442 和 NCT00126594）用于外部验证。反应每 8-12 周被分为进展性疾病 (PD) 和非 PD。在治疗开始时、6-8 周后以及每个第三个月在一个盲实验室测量 GAGome。我们将 GAGome 与反应相关联，并开发了用于将 PD 与非 PD 分类的评分，这些评分用于预测治疗开始时或 6-8 周后的反应。
前瞻性纳入了 50 名 mRCC 患者，他们均接受了酪氨酸激酶抑制剂 (TKI)。PD 与 40%的 GAGome 特征的改变相关。我们开发了血浆、尿液和联合糖胺聚糖进展评分，分别在每次反应评估时通过接受者操作特征曲线 (AUC) 监测 PD，其 AUC 分别为 0.93、0.97 和 0.98。对于内部验证，评分在治疗开始时的 AUC 为 0.66、0.68 和 0.74，在 6-8 周时的 AUC 为 0.76、0.66 和 0.75，预测 PD。对于外部验证，回顾性纳入了 70 名 mRCC 患者，他们均接受了含 TKI 的方案。血浆评分在治疗开始时的 AUC 为 0.90，在 6-8 周时的 AUC 为 0.89。敏感性和特异性的汇总值分别为 58%和 79%。局限性包括探索性研究设计。
GAGome 在与 mRCC 对 TKI 的反应相关的变化，并可能为 mRCC 反应机制提供生物学见解。
