Purpose: To comprehensively analyze
N6-methyladenosine modification patterns in
bladder tumors and to further systematically explore the inherent relationships between these modification patterns and multiomic
tumor characteristics. Materials and Methods: A total of 901
bladder tumor samples, including 405 samples from TCGA database, 188 samples from GSE13507 and 308 samples from GSE32894, were included in this systematic analysis. The
N6-methyladenosine modification patterns were identified utilizing unsupervised clustering analysis. To quantify
N6-methyladenosine modification patterns, the m6Ascore of individual sample was developed using principal component analysis algorithms. Relationships among immune infiltration,
tumor mutation burden, various clinical characteristics, molecular subtypes, and the m6Ascore were systematically analyzed. The guiding value of m6Ascore in
immunotherapy was further validated in an external trial cohort. Genomics of Drug Sensitivity in
Cancer expression references were also utilized to perform drug sensitivity analysis for patients with distinct
m6A modification patterns. Results: We determined three different
N6-methyladenosine modification patterns for 901
bladder tumors. The quantitative m6Ascore of individual sample derived from
N6-methyladenosine modification patterns could play a significant role in predicting overall survival, immune cell infiltration, and classic oncogene mutations. A low m6Ascore combined with high
tumor mutation burden indicated better survival outcomes (p < 0.001). A higher m6Ascore also indicated a higher grade, higher T and N stage, elder ages, higher death rate, and higher PD1/PDL1/CTLA4 expressions (p < 0.01). The Basal type tended to exhibit significantly higher m6Ascores than the
Luminal and Neuronal subtypes. External
immunotherapy cohorts demonstrated that no difference in
therapeutic effects was noted between the high and low m6Ascore groups when anti-PD1
immunotherapy was exclusively administered. When anti-PD1 and anti-CTLA4
immunotherapy were simultaneously administered, the high m6Ascore group had a significantly better prognosis than the low m6Ascore group (p < 0.001). High
m6A groups were potentially sensitive to various medical treatments including
Bleomycin,
Bortezomib,
Cisplatin,
Cyclopamine,
Dasatinib, Docetaxe,
Rapamycin, and
Vinblastine in this study. Conclusions: This study systematically revealed the important roles of
m6A methylation modification patterns in
bladder tumors. Detailed quantification of
m6A modification patterns could improve our understanding of the
bladder tumor microenvironments and could provide guidance for future
immunotherapy strategies.