Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
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Data availability
All data can be downloaded from open databases or from supplementary materials.
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Acknowledgements
Many thanks for the free and open database (TCGA, GEO, TCIA, and Imvigor210).
Funding
This study was supported by the Jiangxi Provincial “Double Thousand Plan” Fund Project (Grant No. jxsq2019201027). Project of Natural Science Foundation of Jiangxi Province (20202BABL206032).
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XL, JZ, BF, SL, YP: Conceptualization, methodology, software, investigation, formal analysis. FZ, SX: Data curation, Writing—original draft; LY, MJ: Visualization, investigation; JL, JD: Resources, supervision.
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432_2023_5067_MOESM1_ESM.rar
Supplementary file1 Figure S1 The graph shows the PCA results when k = 2. Figure S2 Tumor Mutation Burden analysis (C) of BMR score. Table S1 The merged dataset was obtained after removing the batch effect. Table S2 The intersection genes between the dataset and the genes related to butyrate metabolism. Table S3 70 BMR genes were selected via univariate Cox regression analysis. Table S4 The differential expression matrices for different BMR subtypes. Table S5 The results of different expression genes analysis. Table S6 Raw data of Bladder cancer in TCIA dataset. Table S7 Raw data of Bladder cancer in IMvigor210 dataset. Table S8 The butyrate metabolism-related genes were risk factors in BLCA. Table S9 The results of two molecular subtypes, with 317 patients in subtype A and 277 patients in subtype B. Table S10 882 differentially expressed genes (DEGs) through differential analysis to further investigate the potential biological functions of BMR-associated subtypes (RAR 114031 KB)
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Yuan, P., Li, S., **ong, S. et al. Development of a butyrate metabolism-related gene-based molecular subtypes and scoring system for predicting prognosis and immunotherapy response in bladder cancer. J Cancer Res Clin Oncol 149, 12489–12505 (2023). https://doi.org/10.1007/s00432-023-05067-5
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DOI: https://doi.org/10.1007/s00432-023-05067-5