Urine cytologic examination is the most widely used noninvasive pathologic test to screen bladder urothelial carcinoma (BLCA). However, inadequate diagnostic accuracy remains the major challenge to be solved. We performed high-throughput proteomcis in ten paired samples of BLCA and benign urothelial lesion (BUL) to identify ancillary proteomic markers in liquid-based cytology (LBC).
All samples were analyzed by in-depth quantitative protomics mass spectrometry (MS) to indicate differentially expressed proteins (DEP) between two groups. MS data were analyzed using a combination of MaxQuant and Perseus computational platforms, and a total of 4,839 proteins were identified, and 112 DEP were confirmed to be significantly altered proteins in BLCA group compared with BUL group (FDR q value
As a consequence, 12 proteins including ACACA, AHNAK, ATP1A1, DSG1, EIF4A1, EPPK1, HSP90AB1, MYH14, RPS8, TOP2B, TUBB and YWHAZ were identified as putative candidates to apply to immunostaining. To determine immunocytochemical expression in LBC, protein expression was screened according to The Human Protein Atlas and six proteins finally enrolled to validate immunoreactivity in independent LBC cohorts where AHNAK was confirmed a unique intracellular protein translocation in immunostaining depending on tumor or non-tumor cells.
This finding provided a new biomarker which can be applicable to discriminate between BLCA and BUL in LBC. To our knowledge, the present study provides the first evidence of the identification of a clinical biomarker from LBC based on in-depth proteomics.
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All authors have declared no conflicts of interest.