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The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis
Xiangnan Zhang1, Liuxing Wu1,2, Liqing Jia1
1Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Key Laboratory of Prevention and Control of Human Major Diseases, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China.
Abstract:
Previous studies have focused on the impact of individual RNA modifications on tumor development. This study comprehensively investigated the effects of multiple RNA modifications, including m6A, alternative polyadenylation, pseudouridine, adenosine-to-inosine editing, and uridylation, on gastric cancer (GC). By analyzing 1,946 GC samples from eleven independent cohorts, we identified distinct clusters of RNA modification genes with varying survival rates and immunological characteristics. We assessed the chromatin activity of these RNA modification clusters through regulon enrichment analysis. A prognostic model was developed using Stepwise Regression and Random Survival Forest algorithms and validated in ten independent datasets. Notably, the low-risk group showed a more favorable prognosis and positive response to immune checkpoint blockade therapy. Single-cell RNA sequencing confirmed the abundant expression of signature genes in B cells and plasma cells. Overall, our findings shed light on the potential significance of multiple RNA modifications in GC prognosis, stemness development, and chemotherapy resistance.
Insights
This study reveals how multiple RNA modifications impact gastric cancer (GC) development and patient survival. Identifying distinct RNA modification patterns can predict prognosis and guide immune checkpoint blockade therapy for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Previous research examined individual RNA modifications in tumor development.
- Gastric cancer (GC) is a significant global health concern with complex underlying mechanisms.
Purpose of the Study:
- To comprehensively investigate the impact of multiple RNA modifications on gastric cancer.
- To identify RNA modification patterns associated with GC prognosis and immune characteristics.
Main Methods:
- Analysis of 1,946 GC samples across eleven cohorts.
- Regulon enrichment analysis for chromatin activity assessment.
- Development and validation of a prognostic model using Stepwise Regression and Random Survival Forest.
Main Results:
- Distinct clusters of RNA modification genes were identified, correlating with survival rates and immunological features.
- A validated prognostic model differentiated GC patients into risk groups.
- The low-risk group exhibited better prognosis and responsiveness to immune checkpoint blockade therapy.
- Single-cell RNA sequencing showed signature gene enrichment in B cells and plasma cells.
Conclusions:
- Multiple RNA modifications play a significant role in GC prognosis, stemness, and chemotherapy resistance.
- RNA modification patterns offer potential biomarkers for GC patient stratification and treatment selection.
- Findings highlight the interplay between RNA modifications and the tumor immune microenvironment in GC.
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