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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
N6-methyladenosine regulators are potential prognostic biomarkers for multiple myeloma
Jing Wang1,2,3, Yifan Zuo2, Chenglan Lv2
1Department of Oncology and Hematology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, People's Republic of China.
Abstract:
N6-methyladenosine (m6A) regulators play an important role in tumorigenesis; however, their role in multiple myeloma (MM) remains unknown. This study aimed to create an m6A RNA regulators prognostic signature for MM patients. We integrated data from the Multiple Myeloma Research Foundation CoMMpass Study and the Genotype-Tissue Expression database to analyze gene expression profiles of 21 m6A regulators. Consistent clustering analysis was used to identify the clusters of patients with MM having different clinical outcomes. Gene distribution was analyzed using principal component analysis. Next, we generated an mRNA gene signature of m6A regulators using a multivariate logistic regression model with least absolute shrinkage and selection operator. The expressions of m6A regulators, except FMR1, were significantly different in MM samples compared with those in normal samples. The KIAA1429, HNRNPC, FTO, and WTAP expression levels were dramatically downregulated in tumor samples, whereas those of other signatures were remarkably upregulated. Three clusters of patients with MM were identified, and significant differences were found in terms of overall survival (p = .024). A prognostic two-gene signature (KIAA1429 and HNRNPA2B1) was constructed, which had a good prognostic significance using the ROC method (AUC = 0.792). Moreover, the risk score correlated with the infiltration immune cells. In addition, KEGG pathway analysis showed that 16 pathways were dramatically enriched. The m6A signature might be a novel biomarker for predicting the prognosis of patients with MM (p = .002). Our study is the first to explore the potential application value of m6A in MM. These findings may enhance the understanding of the functional organization of m6A in MM and provide new insights into the treatment of MM patients.
Insights
This study identifies N6-methyladenosine (m6A) regulators as potential biomarkers for multiple myeloma (MM). A novel m6A RNA signature accurately predicts MM patient prognosis and correlates with immune cell infiltration, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- N6-methyladenosine (m6A) regulators are implicated in various cancers.
- The role of m6A regulators in multiple myeloma (MM) pathogenesis and prognosis is largely unexplored.
Purpose of the Study:
- To develop a prognostic signature based on m6A RNA regulators for patients with multiple myeloma.
- To investigate the potential of m6A regulators as biomarkers in MM.
Main Methods:
- Integrated gene expression data from MM patients and databases.
- Applied consistent clustering, principal component analysis, and LASSO regression to identify key m6A regulators.
- Constructed a prognostic signature using multivariate logistic regression and validated it with ROC analysis.
Main Results:
- Identified significant differences in m6A regulator expression between MM and normal samples, with notable down/upregulation patterns.
- Discovered three distinct patient clusters with significant differences in overall survival (p=0.024).
- Developed a two-gene prognostic signature (KIAA1429 and HNRNPA2B1) with high predictive accuracy (AUC=0.792), correlating with immune cell infiltration and enriched KEGG pathways.
Conclusions:
- The developed m6A RNA signature serves as a novel and effective biomarker for predicting MM prognosis (p=0.002).
- This research provides the first exploration of m6A regulators' application in MM, enhancing understanding of their functional roles.
- Findings offer new perspectives for MM treatment strategies.

