N6-Methyladenosine Regulators Are Involved in the Progression of and Have Clinical Impact on Breast Cancer
| Autor: | Rui Huang, Yangbao Tao, Chaojing Zheng, Yanni Song, Qian Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Adenosine medicine.medical_treatment AKT1 Breast Neoplasms Cell Cycle Proteins Methylation Risk Assessment Correlation Breast cancer Predictive Value of Tests Internal medicine Consensus clustering Humans Medicine Gene Regulatory Networks Protein Interaction Maps Neoplasm Staging business.industry Proportional hazards model RNA-Binding Proteins Cell Differentiation Chemoradiotherapy Methyltransferases General Medicine Prognosis medicine.disease Drug Resistance Neoplasm Database Analysis Nottingham Prognostic Index Female RNA Splicing Factors Hormone therapy business |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| DOI: | 10.12659/msm.929615 |
| Popis: | BACKGROUND N6-methyladenosine (m⁶A) modification has been widely studied in various cancers, and m6A regulators, such as METTL3, METTL14, WTAP, and YTHDF1, play crucial roles in breast cancer. However, a comprehensive study of m6A regulators in breast cancer is still lacking. MATERIAL AND METHODS Expression data of m⁶A regulators and clinicopathological information were acquired from The Cancer Genome Atlas (TCGA) program. Protein interaction was collected from the STRING database. Data on tumor purity and correlation among m6A regulators were obtained from the TIMER database. LASSO, consensus clustering, and gene set enrichment analysis (GSEA) were used to evaluate the role of m⁶A regulators. Moreover, the prognostic value of m⁶A-related genomic targets in breast cancer was analyzed by Kaplan-Meier analysis and Cox regression models. RESULTS We found most m⁶A regulators were associated with key clinicopathological parameters, such as tumor staging, Nottingham prognostic index (NPI), and cellularity. Also, consensus clustering analysis-based grouping could effectively predict patients' overall survival. Correlation analysis also showed that these regulators interacted with each other. Patients were further split into a high-risk group and low-risk group based on Cox and LASSO analysis. High-risk patients had a significantly worse overall survival than did low-risk patients. Moreover, AKT1 and MYC were enriched in patients in the high-risk group, according to GSEA analysis. The patients in the high-risk group also displayed resistance to chemoradiotherapy or hormone therapy. CONCLUSIONS The m⁶A regulators are critical participants in the development and progression of breast cancer and are likely to be used to predict prognosis and develop treatment strategies. |
| Databáze: | OpenAIRE |
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