Diagnostic and Prognostic Performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) Assay for Detecting Primary and Recurrent Urinary Bladder Cancer

Abstract

Purpose: To evaluate the diagnostic and prognostic performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) in detecting urinary bladder cancer (UBC). Methods: The Integrated Study on Bladder Cancer (n = 571; mean age:69.4 ± 12.2 years) evaluates cross-sectionally SPARC diagnostic performance in primary (n = 264) and recurrent (n = 307) UBC. SPARC prognostic performance is evaluated in a nested cohort (n = 250) prospectively followed for 80 months to detect tumor relapse, recurrence and/or progression. Baseline urine samples are analyzed blindly using a commercially available SPARC ELISA assay, characterized for its analytical performance according to clinical test regulatory requirements (R&D Manufactures Inc.). Results: While higher mean SPARC levels are detected in primary (p = 0.008) and recurrent (p < 0.0001) UBC, the assay has limited diagnostic performance (AUC:0.593; 95% CI:0.524-0.663). SPARC positive patients undergoing disease monitoring are more likely to develop tumor relapse (age and gender Adj. HR:1.52; 95% CI:1.04-2.22) and progression (Adj. HR:1.83; 95% CI:1.02-3.27). However, prognostic performance is affected by hematuria. Conclusions: SPARC diagnostic performance for detecting UBC appears insufficient for clinical implementation. In patients undergoing disease monitoring, SPARC is a promising prognostic marker for tumor relapse and/or progression, but is affected by hematuria.

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers—What Should a Urologist Really Know?

“…Onsidering cellular signaling proteins such as Orsomucoid-1 (acute-phase protein [ 37 ]), Osteonectin, BM40 or Secreted Protein Acidic and Rich in Cystein (SPARC—Extracellular matrix protein that promotes cellular adhesion [ 38 ]), Apurinic/apyrimidinic endonuclease 1/redox factor-1 (DNA repair and activation of transcriptional factors [ 39 ]), soluble Fas (programmed cellular death via Fas/APO-1/CD95 [ 40 ]), Aurora kinase A (AURKA—Assembly of mitotic spindle and facilitation of the mitosis [ 41 ]), Serum Irisin , (activator of gene promoters for the browning of the white adipose tissue [ 42 ]), Amplified in breast cancer 1 (AIB1—Transcriptional activity [ 43 ]) in combination with EIF5A2 (protein synthesis and in translation elongation [ 44 ]), when employed as a diagnostic biomarkers yielded variable sensitivities and specificities, ranging from 39% to 93% and 70% to 94%, respectively [ 45 , 46 ]. Although outperforming urine cytology when it comes to sensitivity, some were largely influenced by the presence of hematuria, or did not achieve satisfactory NPV to be considered for the everyday practice use.…”

Urinary peptide panel for prognostic assessment of bladder cancer relapse

“…Mass spectrometry has been already applied for acquiring BC specific proteomics and metabolomics profiling data and several prognostic markers based on proteomics and metabolomics studies have been reported in the literature, highlighting the value of -omics features in improving BC management. Urine and serum proteomic-based biomarkers, like SPARC 24 , SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) 25 have been recently reported as prognostic markers for BC. Moreover, according to recent metabolomics studies, i.e.…”

SPARC: a potential target for functional nanomaterials and drugs

“…The frequency and strength of SPARC expression negatively correlated with disease-specific survival in human bladder tumor tissues (Said et al, 2013). SPARC shows potential as a prognostic indicator of tumor recurrence or progression during prostate cancer theranostics but is affected by hematuria (Critselis et al, 2019). The level of the SPARC gene has a significant relationship with the histological type, pathological status, and prognosis of bladder cancer (Yamanaka et al, 2001).…”