Journal article
Novel plasma glycoprotein biomarkers predict progression-free survival in surgically resected clear cell renal cell carcinoma
Urologic oncology, Vol.40(4), pp.168.e11-168.e19
04/2022
DOI: 10.1016/j.urolonc.2021.12.005
PMID: 35148948
Abstract
•High-throughput glycoproteomics evaluated differential expression of glycoprotein-isoforms as novel biomarkers.•Glycoprotein isoform differences were measured in serum samples of patients with ccRCC prior to undergoing surgical treatment.•Glycoproteins identified were strongly associated with progression free survival.
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).
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.
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).
Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.
Details
- Title: Subtitle
- Novel plasma glycoprotein biomarkers predict progression-free survival in surgically resected clear cell renal cell carcinoma
- Creators
- Daniel J. Serie - InterScienceAmanda A. Myers - Mayo Clinic in FloridaDaniela A. Haehn - Mayo Clinic in FloridaAlexander S. Parker - Florida CollegeEssa M. Bajalia - Mayo Clinic in FloridaGiovanni A. Gonzalez - Mayo Clinic in FloridaQiongyu Li - InterScienceMaurice Yu Wong - InterScienceKaitlynn C. Moser - InterScienceBo Zhou - InterScienceDavid D. Thiel - Mayo Clinic in Florida
- Resource Type
- Journal article
- Publication Details
- Urologic oncology, Vol.40(4), pp.168.e11-168.e19
- DOI
- 10.1016/j.urolonc.2021.12.005
- PMID
- 35148948
- NLM abbreviation
- Urol Oncol
- ISSN
- 1078-1439
- eISSN
- 1873-2496
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Urology
- Record Identifier
- 9984934671402771
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