Plasma and Urine Free Glycosaminoglycans as Monitoring and Predictive Biomarkers in Metastatic Renal Cell Carcinoma: A Prospective Cohort Study
Journal article, 2023

PURPOSENo 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.PATIENTS AND METHODSWe 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.RESULTSFifty 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.CONCLUSIONGAGomes changed in association with mRCC response to TKIs and may provide biologic insights into mRCC mechanisms of response.

Author

Francesco Gatto

Chalmers, Life Sciences, Systems and Synthetic Biology

Sinisa Bratulic

Chalmers, Life Sciences, Systems and Synthetic Biology

Eric Jonasch

Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Div Canc Med

Angelo Limeta

Chalmers, Life Sciences, Systems and Synthetic Biology

F. Maccari

University of Modena and Reggio Emilia

Fabio Galeotti

University of Modena and Reggio Emilia

Nicola Volpi

University of Modena and Reggio Emilia

Sven Lundstam

University of Gothenburg

Jens B Nielsen

Chalmers, Life Sciences, Systems and Synthetic Biology

Ulrika Stierner

University of Gothenburg

JCO PRECISION ONCOLOGY

2473-4284 (eISSN)

Vol. 7 e2200361

Aurora Life Sciences

VINNOVA (2016-00763), 2016-06-01 -- 2017-05-31.

Region Västra Götaland (2016-01865), 2016-06-01 -- 2017-05-31.

Subject Categories

Urology and Nephrology

Cancer and Oncology

DOI

10.1200/PO.22.00361

PubMed

36848607

More information

Latest update

1/26/2024