Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Bladder
cancer (BCa) is the predominant malignancy of
the urinary
system. Herein, a comprehensive urine proteomic feature was initially
established for the noninvasive diagnosis and recurrence monitoring
of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls
(NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected
to screen urinary protein biomarkers. 4761 and 3668 proteins were
qualified and quantified by DDA and sequential window acquisition
of all theoretical mass spectra (SWATH-MS) analysis in two discovery
sets, respectively. Upregulated proteins were validated by multiple
reaction monitoring (MRM) in two independent combined sets. Using
the multi-support vector machine-recursive feature elimination (mSVM-RFE)
algorithm, a model comprising 13 proteins exhibited good performance
between BCa and NT with an AUC of 0.821 (95% CI: 0.675–0.967),
90.9% sensitivity (95% CI: 72.7–100%), and 73.3% specificity
(95% CI: 53.3–93.3%) in the diagnosis test set. Meanwhile,
an 11-marker classifier significantly distinguished BCR from BCNR
with 75.0% sensitivity (95% CI: 50.0–100%), 81.8% specificity
(95% CI: 54.5–100%), and an AUC of 0.784 (95% CI: 0.609–0.959)
in the test cohort for relapse surveillance. Notably, six proteins
(SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly
reported. This paper reveals novel urinary protein biomarkers for
BCa and offers new theoretical insights into the pathogenesis of bladder
cancer (data identifier PXD044896).