Novel Plasma Glycoprotein Biomarkers Predict Progression-Free Survival in Surgically Resected Clear Cell Renal Cell Carcinoma

Abstract

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

Construction of 2DE-Patterns of Plasma Proteins: Aspect of Potential Tumor Markers

“…(www.preprints.org) | NOT PEER-REVIEWED | Posted: 14 July 2022 doi:10.20944/preprints202207.0208.v1cancer[32]. Differential glycoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of clear cell renal cell carcinoma (ccRCC)[147]. The level of clusterin is enhanced in plasma of patients with BC, CRC, HCC, and B-cell acute lymphoblastic leukemia (B-ALL)[52,58,69,148,149].…”