Abstract
The transition from non–muscle‐invasive bladder cancer (NMIBC) to muscle‐invasive bladder cancer (MIBC) is detrimental to bladder cancer (BLCA) patients. Here, we aimed to study the underlying mechanism of the subtype transition. Gene set variation analysis (GSVA) revealed the epithelial‐mesenchymal transition (EMT) signalling pathway with the most positive correlation in this transition. Then, we built a LASSO Cox regression model of an EMT‐related gene signature in BLCA. The patients with high risk scores had significantly worse overall survival (OS) and disease‐free survival (DFS) than those with low risk scores. The EMT‐related gene signature also performed favourably in the accuracy of prognosis and in the subtype survival analysis. Univariate and multivariate Cox regression analyses demonstrated that the EMT‐related gene signature, pathological N stage and age were independent prognostic factors for predicting survival in BLCA patients. Furthermore, the predictive nomogram model was able to effectively predict the outcome of BLCA patients by appropriately stratifying the risk score. In conclusion, we developed a novel EMT‐related gene signature that has tumour‐promoting effects, acts as a negative independent prognostic factor and might facilitate personalized counselling and treatment in BLCA.
Highlights
Bladder cancer (BLCA) is a urinary tract malignancy with an estimated 549 000 new cases and 200 000 deaths reported in 2018 and ranks the 10th most common form of cancer worldwide.[1]
We found that the epithelial‐mesenchymal transition (EMT) signalling pathway was the most highly enriched pathway in the BLCA subtype transition from non– muscle‐invasive bladder cancer (NMIBC) to muscle‐invasive bladder cancer (MIBC) by using data from several cohorts in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets
MIBC seems to originate from flat dysplasia and carcinoma in situ (CIS) and is genetically unstable and shows a high risk of progression and metastasis.[22]
Summary
Bladder cancer (BLCA) is a urinary tract malignancy with an estimated 549 000 new cases and 200 000 deaths reported in 2018 and ranks the 10th most common form of cancer worldwide.[1]. Patients with MIBC have a less favourable prognosis, with a five‐year survival rate of
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