Abstract
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.
Highlights
Urothelial carcinoma of the bladder (UCB) is the 10th most common cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths per year [1]
We investigated the association of the mRNA expression of suggested surrogate markers for the basal (KRT5) and luminal (FOXA1, GATA3, KRT20, androgen receptor (AR)) subtypes of muscle-invasive bladder cancer (MIBC) with clinical and pathological characteristics and survival
The cohort was stratified into patients with high or low marker expression using the median mRNA expression of KRT5, KRT20, FOXA1, GATA3, and AR as objective cut-offs
Summary
Urothelial carcinoma of the bladder (UCB) is the 10th most common cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths per year [1]. Radical cystectomy is associated with high rates of perioperative morbidity and mortality [5], and approximately 50% of patients experience distant disease recurrence after cystectomy, mostly within the first two years, later recurrences have been reported [6,7,8]. The need for lifelong surveillance as well as high treatment costs result in UCB being the most expensive cancer per patient from diagnosis to death in the US [9,10,11]. Given the high costs and poor outcome of patients with UCB, there is a high demand for novel molecular markers to improve diagnostics and serve as targets for new therapies
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