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Published on: March 30, 2019
Dysfunctions associated with methylation, microRNA expression and gene expression in lung cancer
Tao Huang1, Min Jiang, Xiangyin Kong
1Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Abstract:
Integrating high-throughput data obtained from different molecular levels is essential for understanding the mechanisms of complex diseases such as cancer. In this study, we integrated the methylation, microRNA and mRNA data from lung cancer tissues and normal lung tissues using functional gene sets. For each Gene Ontology (GO) term, three sets were defined: the methylation set, the microRNA set and the mRNA set. The discriminating ability of each gene set was represented by the Matthews correlation coefficient (MCC), as evaluated by leave-one-out cross-validation (LOOCV). Next, the MCCs in the methylation sets, the microRNA sets and the mRNA sets were ranked. By comparing the MCC ranks of methylation, microRNA and mRNA for each GO term, we classified the GO sets into six groups and identified the dysfunctional methylation, microRNA and mRNA gene sets in lung cancer. Our results provide a systematic view of the functional alterations during tumorigenesis that may help to elucidate the mechanisms of lung cancer and lead to improved treatments for patients.
Insights
This study integrates multi-omics data, including methylation, microRNA, and mRNA, to identify key molecular pathways in lung cancer. The findings reveal specific dysfunctional gene sets, offering insights into tumorigenesis and potential therapeutic targets.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Understanding complex diseases like cancer requires integrating high-throughput data from various molecular levels.
- Lung cancer pathogenesis involves intricate molecular alterations across different biological layers.
Purpose of the Study:
- To integrate methylation, microRNA, and mRNA data to identify dysfunctional gene sets in lung cancer.
- To systematically analyze functional alterations during tumorigenesis using multi-omics data.
Main Methods:
- Integration of methylation, microRNA, and mRNA data from lung cancer and normal tissues using Gene Ontology (GO) functional gene sets.
- Evaluation of discriminating ability for each gene set using Matthews correlation coefficient (MCC) via leave-one-out cross-validation (LOOCV).
- Ranking of MCCs for methylation, microRNA, and mRNA sets per GO term to classify and identify dysfunctional gene sets.
Main Results:
- Identification of six groups of GO sets based on comparative MCC ranks of methylation, microRNA, and mRNA.
- Pinpointing specific dysfunctional methylation, microRNA, and mRNA gene sets implicated in lung cancer development.
- A systematic overview of functional alterations during lung cancer progression.
Conclusions:
- The integrated multi-omics approach provides a comprehensive view of functional changes in lung cancer.
- Identified dysfunctional gene sets can elucidate lung cancer mechanisms.
- Findings may contribute to developing improved diagnostic and therapeutic strategies for lung cancer patients.
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