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Published on: January 21, 2020
Screening candidate microRNA-mRNA network for predicting the response to chemoresistance in osteosarcoma by
Penggao Dai1, Yancheng He1, Guosong Luo2
1College of Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
Abstract:
The search for biomarkers is important for providing more targeted treatments for osteosarcoma patients with chemoresistance. In this study, differentially expressed microRNAs (miRNAs) were identified from miRNA expression profiles. And the target messenger RNAs (mRNAs) of miRNA were obtained from two websites in public domains. Analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway by these miRNA targets suggests that they may have potential links to osteosarcoma chemoresistance. In the protein-protein interaction (PPI) network, we screened three subnetworks and 10 hub RNAs, and analyzed through KEGG pathway and searched the PubMed database, indicating that they were significantly associated with drug resistance. Then we found 12 key mRNAs by analyzing the mRNA expression profile. Survival analyses showed that most of the 10 hub mRNAs and 12 key mRNAs had a significant influence on the prognosis of patients with chemoresistance osteosarcoma. A miRNA-mRNA network is constructed by integrating mRNAs and miRNAs information. The network biomarkers in this study have an advantage over traditional single-molecule biomarkers in terms of predictive power. And the mRNAs in this network biomarkers are supported by survival analysis or by existing theories. These results will contribute to the choice of chemotherapy before treatment and the prediction of patient prognosis.
Insights
This study identifies novel microRNA (miRNA) and messenger RNA (mRNA) network biomarkers for predicting chemoresistance in osteosarcoma patients. These biomarkers offer improved predictive power for targeted treatments and patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Osteosarcoma chemoresistance necessitates novel biomarkers for effective treatment strategies.
- MicroRNAs (miRNAs) and messenger RNAs (mRNAs) play crucial roles in cancer progression and drug response.
Purpose of the Study:
- To identify and validate network biomarkers involving miRNAs and mRNAs associated with osteosarcoma chemoresistance.
- To explore the potential of these biomarkers in predicting patient prognosis and guiding chemotherapy decisions.
Main Methods:
- Differential expression analysis of miRNA and mRNA profiles.
- Bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction.
- Survival analysis to assess the prognostic significance of identified biomarkers.
Main Results:
- Identified differentially expressed miRNAs and their target mRNAs linked to osteosarcoma chemoresistance.
- Screened subnetworks and hub RNAs within the PPI network, showing significant association with drug resistance.
- Discovered 12 key mRNAs and confirmed that most identified hub and key mRNAs significantly influenced patient prognosis.
- Constructed a comprehensive miRNA-mRNA network, demonstrating superior predictive power compared to single-molecule biomarkers.
Conclusions:
- The developed miRNA-mRNA network biomarkers show promise for predicting osteosarcoma chemoresistance and patient outcomes.
- These findings can aid in selecting appropriate chemotherapy regimens and improving prognostic predictions for osteosarcoma patients.
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