Integrated molecular analyses of an interferon-γ based subtype with regard to outcome, immune characteristics, and immunotherapy in bladder cancer and experimental verification

Abstract

This study attempted to explore the role of interferon-γ related genes (IRGs) in the prognosis and immunotherapy of bladder cancer (BC). Based on data downloaded from public databases, molecular subtypes with different IRG expression patterns were determined via nonnegative matrix factorization clustering. On the basis of IRGs, interferon-γ related gene signature (IRGS) was developed through Cox regression analyses. We identified that two molecular subgroups with different outcome and immune profiles. It was proved that IRGS possessed prediction efficiency for BC prognosis. Compared with low IRGS group, high IRGS group was related to less anti-cancer immune cells infiltration, less tumor mutation burden score, more cancer stem cell index, and less benefit from immunotherapy. Differential expression of six model genes (IRF5, LATS2, MTHFD2, VAMP8, HLA-G and PTPN6) was validated between paired tissues by RT-qPCR. This study presents a prognostic model, which could serve as an indicator for the benefit of BC immunotherapy.