Novel plasma glycoprotein biomarkers predict progression-free survival in surgically resected clear cell renal cell carcinoma

Daniel J. Serie, Amanda A. Myers, Daniela A. Haehn, Alexander S. Parker, Essa M. Bajalia, Giovanni A. Gonzalez, Qiongyu Li, Maurice Yu Wong, Kaitlynn C. Moser, Bo Zhou, David D. Thiel

Research output: Contribution to journalArticlepeer-review


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 Harrell's 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 (HR) 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 to 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.

Original languageEnglish (US)
Pages (from-to)168.e11-168.e19
JournalUrologic Oncology: Seminars and Original Investigations
Issue number4
StatePublished - Apr 2022


  • Biomarker
  • Glycoproteins
  • Progression free survival
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology


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