Development of a butyrate metabolism-related gene-based molecular subtypes and scoring system for predicting prognosis and immunotherapy response in bladder cancer.

Abstract

In recent times, multiple molecular subtypes with varying prognoses have been identified in bladder cancer (BLCA). However, the attributes of butyrate metabolism-related (BMR) molecular subtypes and their correlation with immunotherapy response remain inadequately explored in BLCA. We utilized 594 samples of BLCA to investigate the molecular subtypes mediated by BMR genes and their correlation with the immunotherapy response. To quantify the BMR features of individual tumors, we developed a BMR score through the COX and LASSO regression methods. Clinical-related, tumor microenvironment, drug-sensitive and immunotherapy analyses were used to comprehensively analyze BMR scores. Two distinct molecular subtypes related to butyrate metabolism were identified in BLCA, each with unique prognostic implications and immune microenvironments. BMR score was constructed based on 7 BMR genes and was used to classify the patients into two score groups. Clinical analysis revealed that the BMR score was an independent prognostic factor. The higher the score, the worse the prognosis. The BMR score can also predict tumor immunity. The results demonstrated that a low BMR score was associated with higher efficacy of immunotherapy, which was also validated by an external dataset. Our study proposes both molecular subtypes and a BMR-based score as promising prognostic classifications in BLCA. These findings may offer new insights for the development of precise targeted cancer therapies.