Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis

Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlat...

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Autores principales:	Antonio Lopez-Beltran, Ana Blanca, Alessia Cimadamore, Rajan Gogna, Rodolfo Montironi, Liang Cheng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bladder cancer molecular taxonomy molecular classification NanoString luminal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1776742134fa4f18a8f9f619a18e0621
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spelling	oai:doaj.org-article:1776742134fa4f18a8f9f619a18e06212021-11-11T15:33:45ZMolecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis10.3390/cancers132155002072-6694https://doaj.org/article/1776742134fa4f18a8f9f619a18e06212021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5500https://doaj.org/toc/2072-6694Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four-gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString-based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/-/KRT20low/-) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14-/KRT5-/GATA3-/KRT20-), null/double negative (non-luminal/non-basal). These three categories were meaningful in terms of overall cancer-specific survival (<i>p </i>< 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (<i>p </i>< 0.0001), NMIBC vs. MIBC (<i>p </i>< 0.001), or by AJCC stage category Ta (<i>p </i>= 0.0012) and T1 (<i>p </i>< 0.0001) but did not reach significance in T2-T4 (<i>p </i>= 0.563). PD-L1 expression (low vs. high) was also different according to molecular subtype, with high PD-L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (<i>p </i>= 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer-specific survival (<i>p </i>< 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer-specific survival (<i>p </i>< 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and affordable tool in this rapidly expanding area of precision genomics.Antonio Lopez-BeltranAna BlancaAlessia CimadamoreRajan GognaRodolfo MontironiLiang ChengMDPI AGarticlebladder cancermolecular taxonomymolecularclassificationNanoStringluminalNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5500, p 5500 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer molecular taxonomy molecular classification NanoString luminal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	bladder cancer molecular taxonomy molecular classification NanoString luminal Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Antonio Lopez-Beltran Ana Blanca Alessia Cimadamore Rajan Gogna Rodolfo Montironi Liang Cheng Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
description	Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four-gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString-based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/-/KRT20low/-) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14-/KRT5-/GATA3-/KRT20-), null/double negative (non-luminal/non-basal). These three categories were meaningful in terms of overall cancer-specific survival (<i>p </i>< 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (<i>p </i>< 0.0001), NMIBC vs. MIBC (<i>p </i>< 0.001), or by AJCC stage category Ta (<i>p </i>= 0.0012) and T1 (<i>p </i>< 0.0001) but did not reach significance in T2-T4 (<i>p </i>= 0.563). PD-L1 expression (low vs. high) was also different according to molecular subtype, with high PD-L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (<i>p </i>= 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer-specific survival (<i>p </i>< 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer-specific survival (<i>p </i>< 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and affordable tool in this rapidly expanding area of precision genomics.
format	article
author	Antonio Lopez-Beltran Ana Blanca Alessia Cimadamore Rajan Gogna Rodolfo Montironi Liang Cheng
author_facet	Antonio Lopez-Beltran Ana Blanca Alessia Cimadamore Rajan Gogna Rodolfo Montironi Liang Cheng
author_sort	Antonio Lopez-Beltran
title	Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
title_short	Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
title_full	Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
title_fullStr	Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
title_full_unstemmed	Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
title_sort	molecular classification of bladder urothelial carcinoma using nanostring-based gene expression analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1776742134fa4f18a8f9f619a18e0621
work_keys_str_mv	AT antoniolopezbeltran molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis AT anablanca molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis AT alessiacimadamore molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis AT rajangogna molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis AT rodolfomontironi molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis AT liangcheng molecularclassificationofbladderurothelialcarcinomausingnanostringbasedgeneexpressionanalysis
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Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis

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