Abstract

BackgroundThis study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy.MethodsIHC was performed on tumor specimens from 366 patients with transitional cell bladder cancer. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to develop a multi-marker classifier for predicting DFS of patients with bladder cancer. The Kaplan–Meier estimate was performed to assess DFS, and unadjusted and adjusted Cox regression models were used to identify independent risk factors to predict DFS of patients with bladder cancer.ResultsBased on the LASSO Cox regression model, nine prognostic markers were identified in the training cohort. Patients were stratified into low- and high-risk groups using the IHC-based classifier. In the training cohort, the 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the high-risk group (p < 0.001). Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics. Finally, a nomogram comprising the classifier and clinicopathological factors was developed for clinical application.ConclusionThe nine-IHC-based classifier is a reliable prognostic tool, which can eventually guide clinical decision making regarding treatment strategy and follow-up scheduling of bladder cancer.

Highlights

  • This study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy

  • The 10-year DFS was significantly better in low-risk patients (71%) compared with high-risk patients (18%) (p < 0.001); in the validation cohort, the 10-year DFS was 86% for the low-risk group and 20% for the highrisk group (p < 0.001)

  • Multivariable Cox regression analyses showed that the high-risk group based on the classifier was associated with poorer DFS adjusted by clinicopathological characteristics

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Summary

Introduction

This study aimed to assess the prognostic value of various diagnostic immunohistochemical (IHC) markers and develop an IHC-based classifier to predict the disease-free survival (DFS) of patients with bladder cancer undergoing radical cystectomy. Bladder cancer is currently the 10th most commonly diagnosed malignancy worldwide, accounting for 549,393 new cases and 199,922 deaths in 2018 [1,2,3]. 70% of patients are diagnosed with non-muscle-invasive bladder cancer (NMIBC), whereas the remaining have muscle-invasive bladder cancer (MIBC). For MIBC, radical cystectomy is considered as the standard treatment choice; neoadjuvant chemotherapy is used in MIBC to improve the survival of patients [5]. Despite the aggressive treatment strategy, the 5-year overall survival (OS) rate for MIBC is approximately 50% [6, 7]. There still exist undefined molecular mechanism that promotes the tumorigenesis and progression of bladder cancer

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