227P - Proteomic analysis of urothelial lesions reveals novel diagnostic biomarkers to distinguish pathologic pitfalls and protein-protein interactions

Background

Even though patients with non-muscle invasive urothelial carcinoma (NMIUC) show favorable survival rates, more than a half of them relapse during follow-up, while up to 20% progress to muscle-invasive urothelial carcinoma (MIUC). As the presence of invasion confers significant prognostic and therapeutic implications for these patients, its accurate detection is imperative; this has prompted the search for biomarkers predictive of invasion, using mostly genomic analysis. In contrast to the extensive genome-based research published so far in the field of BUC, studies utilizing in-depth proteomic analysis on patient-derived tissue samples, directed toward the identification of biomarkers predictive of tumor invasion, have barely been performed.

Methods

A total of 265 radical cystectomy specimens were selected from the Department of Pathology, Seoul National University Hospital (SNUH). This cohort consisted of 39 formalin-fixed paraffin embedded (FFPE) whole tissue samples used for the in-depth proteomics analysis, besides 226 BUC cases processed and analyzed as tissue microarrays (TMAs) to validate the in-depth proteomics findings along with in vitro testsFor proteomic analysis, 31 tissue specimens, consisting of 9 IUP, 12 PUC, and 10 normal urothelium (NU), were included. Machine learning-based feature selection for candidate markers For validation of IUP, we performed immunohistochemical staining in an independent valid. ation cohort composed of 25 IUP and 16 PUC with inverted growth.

Results

Validation of TUBB6 and TGFBI as potential predictive markers of muscle-invasive urothelial carcinoma (MIUC) and prognosis determinants. tubulin beta 6 class V (TUBB6) and TGFBI mRNA high expression and TUBB6 and TGFBI protein expression levels among NMIUC (pTa/pT1) and MIUC (pT2-pT4) (SNUH). From the overall proteomic landscape, The immunohistochemical validation PYGB as a specific biomarker to distinguish between IUP and PUC with inverted growth.

Conclusions

We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients. We suggest PYGB as a promising immunohistochemical marker for IUP diagnosis in routine practice.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.