Transcriptional profiling of muscle-invasive bladder cancer (MIBC) using RNA sequencing (RNA-seq) technology has demonstrated the existence of intrinsic basal and luminal molecular subtypes that vary in their prognosis and response to therapy. However, routine use of RNA-seq in a clinical setting is restricted by cost and technical difficulties. Herein, we provide a single-sample NanoString-based seven-gene (KRT5, KRT6C, SERPINB13, UPK1A, UPK2, UPK3A and KRT20) MIBC molecular classifier that assigns a luminal and basal molecular subtype. The classifier was developed in a series of 138 chemotherapy naïve MIBCs split into training (70%) and testing (30%) datasets. Further, we validated the previously published CK5/6 and GATA3 immunohistochemical classifier which showed high concordance of 96.9% with the NanoString-based gene expression classifier. Immunohistochemistry-based molecular subtypes significantly correlated with recurrence-free survival (RFS) and disease-specific survival (DSS) in univariable (p = 0.006 and p = 0.011, respectively) and multivariate cox regression analysis for DSS (p = 0.032). Used sequentially, the immunohistochemical- and NanoString-based classifiers provide faster turnaround time, lower cost per sample and simpler data analysis for ease of clinical implementation in routine diagnostics.
Cancers. 2022 Oct 07*** epublish ***
Ekaterina Olkhov-Mitsel, Yanhong Yu, Katherine Lajkosz, Stanley K Liu, Danny Vesprini, Christopher G Sherman, Michelle R Downes
Division of Anatomic Pathology, Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada., Department of Biostatistics, Princess Margaret Hospital, Toronto, ON M5G 2C1, Canada., Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.