mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Eckstein, Markus; Wirtz, Ralph M.; Gross-Weege, Matthias; Breyer, Johannes; Otto, Wolfgang; Stoehr, Robert; Sikic, Danijel; Keck, Bastian; Eidt, Sebastian; Burger, Maximilian; Bolenz, Christian; Nitschke, Katja; Porubský, Štefan; Hartmann, Arndt; Erben, Philipp

doi:10.3390/ijms19113396

Cited by 35 publications

(43 citation statements)

References 45 publications

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“…Also, KRT5 is highly upregulated in basal and KRT20 in luminal subtype in BLCA [6]. qPCR-based molecular subtyping of BLCA by KRT5 and KRT20 mRNA expression is a method associated with the survival of patients with MIBC [43]. It is confirmed that KRT5 and KRT20 showed significant association with ANLN and TLE2 in the Mannheim cohort.…”

Section: Discussionmentioning

confidence: 62%

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

Nitschke

Heinkele

et al. 2019

Cancers

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Anilin actin binding protein (ANLN) and transducing-like enhancer protein 2 (TLE2) are associated with cancer patient survival and progression. The impact of their gene expression on progression-free survival (PFS) of patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) and subtype association has not yet been investigated. qRT-PCR was used to measure the transcript levels of ANLN and TLE2 in the Mannheim cohort, and validated in silico by The Cancer Genome Atlas (TCGA) cohort. Uni-and multivariate Cox regression analyses identified predictors for disease-specific survival (DSS) and overall survival (OS). In the Mannheim cohort, tumors with high ANLN expression were associated with lower OS and DSS, while high TLE2 expression was associated with a favorable OS. The TCGA cohort confirmed that high ANLN and low TLE2 expression was associated with shorter OS and disease-free survival (DFS). In both cohorts, multivariate analyses showed ANLN and TLE2 expression as independent outcome predictors. Furthermore, ANLN was more highly expressed in cell lines and patients with the basal subtype, while TLE2 expression was higher in cell lines and patients with the luminal subtype. ANLN and TLE2 are promising biomarkers for individualized bladder cancer therapy including cancer subclassification and informed MIBC prognosis.

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Section: Discussionmentioning

confidence: 62%

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

Nitschke

Heinkele

et al. 2019

Cancers

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“…The keratin 5 gene, KRT5, is amongst the upregulated genes in urine from bladder cancer patients compared to healthy volunteers. The presence of KRT5 mRNA in tumor tissue has been studied to subclassify muscle-invasive bladder cancers according to therapy response and patient outcome 38 . In CSF from glioblastoma patients, only 2 mRNAs are significantly upregulated compared to CSF from hydrocephalus patients.…”

Section: Assessment Of the Tissues Of Origin And Deconvolution Of Panmentioning

confidence: 99%

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Hulstaert

Morlion

Cobos

et al. 2019

Preprint

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Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease.Where most studies focus on plasma or serum, other biofluids may contain more informative RNA molecules, depending on the type of disease. Here, we present an unprecedented atlas of messenger, circular and small RNA transcriptomes of a comprehensive collection of 20 different human biofluids. By means of synthetic spike-in controls, we compared RNA content across biofluids, revealing a more than 10 000-fold difference in RNA concentration. The circular RNA fraction is increased in nearly all biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. In addition, a subset of biofluids, including stool, sweat, saliva and sputum, contains high levels of bacterial RNAs. Our atlas enables a more informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Taken together, our results reveal novel insights in the RNA content of human biofluids and may serve as a valuable resource for future biomarker studies.

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“…A reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR)-based assessment was used for the objective quantification of FOXA1, GATA3, and AR mRNA expression, as previously described and performed with KRT5 and KRT20 [22,25]. In brief, RNA was extracted from a single 10-µm section of formalin-fixed paraffin embedded (FFPE) routine tissue using a commercially available bead-based extraction method (Xtract ® kit; STRATIFYER Molecular Pathology GmbH, Cologne, Germany).…”

Section: Assessment Of Mrna Expression By Rt-qpcrmentioning

confidence: 99%

“…One-step RT-qPCR was applied for the relative quantification of the mRNA expression of the genes of interest (FOXA1, GATA3 and AR) as well as the reference gene (Calmodulin 2 (CALM2)) by gene-specific TaqMan ® -based assays using the SuperScript III PLATINUM One-Step, quantitative RT-PCR System (Invitrogen, Karlsruhe, Germany) on a Stratagene Mx3005p system (Agilent Technologies, Böblingen, Germany) with 30 minutes at 50 • C, two minutes at 95 • C, followed by 40 cycles of 15 seconds at 95 • C and 30 seconds at 60 • C as described previously [22,25].…”

Section: Assessment Of Mrna Expression By Rt-qpcrmentioning

confidence: 99%

“…In an attempt to further reduce the required marker panel, we previously analyzed the prognostic relevance of the mRNA expression of KRT5 and KRT20 as surrogate markers for the basal and luminal subtypes of UCB, respectively [22,23]. However, it remains unclear if such a reduced marker panel adequately mirrors subtypes defined by larger marker panels.…”

Section: Introductionmentioning

confidence: 99%

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FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

Sikic

Eckstein

Wirtz³

et al. 2020

JCM

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It remains unclear how to implement the recently revealed basal and luminal subtypes of muscle-invasive bladder cancer (MIBC) into daily clinical routine and whether molecular marker panels can be reduced. The mRNA expression of basal (KRT5) and luminal (FOXA1, GATA3, KRT20) markers was measured by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to clinicopathological features, recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) in 80 patients with MIBC who underwent radical cystectomy. Additionally, the correlation of single markers with the basal and non-basal subtypes defined by a 36-gene panel was examined and then validated in the TCGA (The Cancer Genome Atlas) cohort. High expression of FOXA1 (p = 0.0048) and KRT20 (p = 0.0317) was associated with reduced RFS. In the multivariable analysis, only FOXA1 remained an independent prognostic marker for DFS (p = 0.0333) and RFS (p = 0.0310). FOXA1 expression (AUC = 0.79; p = 0.0007) was closest to the combined marker expression (AUC = 0.79; p = 0.0015) in resembling the non-basal subtype defined by the 36-gene panel. FOXA1 in combination with KRT5 may be used to distinguish the basal and non-basal subtypes of MIBC.

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mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Cited by 35 publications

References 45 publications

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

FOXA1 Gene Expression for Defining Molecular Subtypes of Muscle-Invasive Bladder Cancer after Radical Cystectomy

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