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Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer

Authors
 Bohyun Kim  ;  Minsun Jung  ;  Kyung Chul Moon  ;  Dohyun Han  ;  Kwangsoo Kim  ;  Hyeyoon Kim  ;  Sunah Yang  ;  Dongjoo Lee  ;  Hyeji Jun  ;  Kyung-Min Lee  ;  Cheng Hyun Lee  ;  Ilias P Nikas  ;  Sohyeon Yang  ;  Hyebin Lee  ;  Han Suk Ryu 
Citation
 INTERNATIONAL JOURNAL OF CANCER, Vol.152(2) : 320-330, 2023-01 
Journal Title
INTERNATIONAL JOURNAL OF CANCER
ISSN
 0020-7136 
Issue Date
2023-01
MeSH
Biomarkers ; Carcinoma, Transitional Cell* ; Humans ; Muscles ; Prognosis ; Proteomics ; RNA, Messenger / genetics ; Tubulin / genetics ; Urinary Bladder Neoplasms* / genetics
Keywords
biomarker ; bladder urothelial carcinoma ; immunohistochemistry ; proteomics ; tubulin beta 6 class V (TUBB6)
Abstract
Muscle-invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high-throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in-house patient-derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform-based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype (TUBB6 migration, P = .0509 and P < .0001; invasion, P = .0002 and P = .0044; TGFBI migration, P = .0214 and P = .0026; invasion, P < .0001 and P = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein-based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P < .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.
Full Text
https://onlinelibrary.wiley.com/doi/10.1002/ijc.34265
DOI
10.1002/ijc.34265
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Jung, Minsun(정민선) ORCID logo https://orcid.org/0000-0002-8701-4282
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193508
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