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Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

View Article: PubMed Central - PubMed

ABSTRACT

Background: The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic-targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans (GAGs) aggregated into diagnostic scores correlated with ccRCC prognosis.

Methods: Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled, and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous (“Low” vs. “High”) or a continuous variable in a multivariate survival analysis.

Results: The survival difference between “High”- vs. “Low”-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3 vs. 100%, p = 3 × 10−4 and 2-year OS rate = 73.3 vs. 100%, p = 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60 vs. 84%, p = 0.0591 and 2-year OS rate = 66.7 vs. 90%, p = 0.0206). In multivariate analysis, the urine biomarker score as a continuous variable was an independent predictor of PFS [hazard ratio (HR): 4.62, 95% CI: 1.66–12.83, p = 0.003] and OS (HR: 10.13, 95% CI: 1.80–57.04, p = 0.009).

Conclusion: This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted.

No MeSH data available.


Kaplan–Meier curves for PFS (left) or OS (right) in ccRCC patients according to urine biomarker score level. The prospective cohort of patients (N = 29) was classified as 14 “Low” (solid) vs. 15 “High” (dashed) biomarker score at the time of sampling.
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Figure 1: Kaplan–Meier curves for PFS (left) or OS (right) in ccRCC patients according to urine biomarker score level. The prospective cohort of patients (N = 29) was classified as 14 “Low” (solid) vs. 15 “High” (dashed) biomarker score at the time of sampling.

Mentions: Kaplan–Meier survival plots for all 31 patients revealed that “Low”-scored patients fared better both in terms of PFS and OS than “High”-scored patients, both in the case of urine and plasma scores. Notably, despite the limited sample size, the difference between “High” vs. “Low” scores was statistically significant in the case of urine [2-year PFS rate = 53.3 (95% CI: 33.2–85.6%) vs. 100% (Not estimable), log-rank test p = 3 × 10−4 and 2-year OS rate = 73.3 (54.0–99.5%) vs. 100% (Not estimable), p = 0.0078, Figure 1] as well as in the case of OS for plasma [2-year PFS rate = 60 (39.7–90.7%) vs. 84% (66–100%), p = 0.0591 and 2-year OS rate = 66.7 (46.6–95.3%) vs. 90% (73.2–100%), p = 0.0206, Figure 2]. When modeled as continuous variables, both scores showed a linear and concordant increase in the risk of both PFS and OS, albeit significant only in the case of urine scores [hazard ratio (HR): 10.13, 95% CI: 1.80–57.04, p = 0.009 and Dxy = 0.66 for OS; HR: 4.62, 95% CI: 1.66–12.83, p = 0.003 and Dxy = 0.57 for PFS]. Estimates for the univariate analysis are reported in Table 2 for PFS and Table 3 for OS.


Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma
Kaplan–Meier curves for PFS (left) or OS (right) in ccRCC patients according to urine biomarker score level. The prospective cohort of patients (N = 29) was classified as 14 “Low” (solid) vs. 15 “High” (dashed) biomarker score at the time of sampling.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5121125&req=5

Figure 1: Kaplan–Meier curves for PFS (left) or OS (right) in ccRCC patients according to urine biomarker score level. The prospective cohort of patients (N = 29) was classified as 14 “Low” (solid) vs. 15 “High” (dashed) biomarker score at the time of sampling.
Mentions: Kaplan–Meier survival plots for all 31 patients revealed that “Low”-scored patients fared better both in terms of PFS and OS than “High”-scored patients, both in the case of urine and plasma scores. Notably, despite the limited sample size, the difference between “High” vs. “Low” scores was statistically significant in the case of urine [2-year PFS rate = 53.3 (95% CI: 33.2–85.6%) vs. 100% (Not estimable), log-rank test p = 3 × 10−4 and 2-year OS rate = 73.3 (54.0–99.5%) vs. 100% (Not estimable), p = 0.0078, Figure 1] as well as in the case of OS for plasma [2-year PFS rate = 60 (39.7–90.7%) vs. 84% (66–100%), p = 0.0591 and 2-year OS rate = 66.7 (46.6–95.3%) vs. 90% (73.2–100%), p = 0.0206, Figure 2]. When modeled as continuous variables, both scores showed a linear and concordant increase in the risk of both PFS and OS, albeit significant only in the case of urine scores [hazard ratio (HR): 10.13, 95% CI: 1.80–57.04, p = 0.009 and Dxy = 0.66 for OS; HR: 4.62, 95% CI: 1.66–12.83, p = 0.003 and Dxy = 0.57 for PFS]. Estimates for the univariate analysis are reported in Table 2 for PFS and Table 3 for OS.

View Article: PubMed Central - PubMed

ABSTRACT

Background: The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic-targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans (GAGs) aggregated into diagnostic scores correlated with ccRCC prognosis.

Methods: Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled, and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous (“Low” vs. “High”) or a continuous variable in a multivariate survival analysis.

Results: The survival difference between “High”- vs. “Low”-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3 vs. 100%, p = 3 × 10−4 and 2-year OS rate = 73.3 vs. 100%, p = 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60 vs. 84%, p = 0.0591 and 2-year OS rate = 66.7 vs. 90%, p = 0.0206). In multivariate analysis, the urine biomarker score as a continuous variable was an independent predictor of PFS [hazard ratio (HR): 4.62, 95% CI: 1.66–12.83, p = 0.003] and OS (HR: 10.13, 95% CI: 1.80–57.04, p = 0.009).

Conclusion: This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted.

No MeSH data available.