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Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia
Hao Zhang1, Liqin Cheng2, Cong Liu3
1Beijing Shijitan Hospital Affiliated to Capital University of Medical Sciences, Neonatology, No. 10 Tieyi Road, Yanggang Store, Haidian District, Beijing 100038, China.
Insights
This study identifies key genes and a ceRNA network impacting pediatric acute myeloid leukemia (AML) survival. These findings offer potential new prognostic indicators and therapeutic targets for childhood AML.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Pediatric acute myeloid leukemia (AML) has a poor prognosis, necessitating novel targeted therapies.
- Current understanding of prognostic biomarkers in pediatric AML requires further development.
- The Cancer Genome Atlas (TCGA) database provides valuable data for molecular profiling.
Purpose of the Study:
- To identify long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) significantly associated with overall survival (OS) in pediatric AML patients.
- To construct a competing endogenous RNA (ceRNA) regulatory network for potential therapeutic targets.
- To evaluate the prognostic value of identified genes using risk scores and nomograms.
Main Methods:
- Utilized TCGA data for pediatric AML patients, including expression profiles and survival information.
- Applied Cox regression analysis to identify OS-related genes (lncRNAs, mRNAs, miRNAs).
- Performed enrichment analysis, protein-protein interaction (PPI) network construction, and ceRNA network establishment.
Main Results:
- Identified 5275 lncRNAs, 176 miRNAs, and 6221 mRNAs significantly affecting pediatric AML prognosis.
- OS-related mRNAs are primarily involved in ribosome, RNA transport, and spliceosome pathways.
- A ceRNA network including NCBP2, RPLP0, UBC, RPS2, and RPS9 was constructed, with NCBP2 as a potential risk factor and others as protective factors.
Conclusions:
- Five gene signals were identified as novel prognostic indicators for pediatric AML survival.
- The constructed ceRNA regulatory network presents a promising new therapeutic target for pediatric AML treatment.
- This research contributes to improving risk stratification and treatment strategies for childhood AML.
Abstract:
Acute myeloid leukemia (AML) in children refers to a malignant tumor caused by the abnormal proliferation of immature myeloid cells in the bone marrow and peripheral blood. The prognosis of patients with pediatric acute myeloid leukemia (AML) remains poor, highlighting the need for improved targeted therapy. The expression data of lncRNAs, mRNAs, and miRNAs and survival information of pediatric AML patients were collected from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was used to screen the lncRNAs, mRNAs, and miRNAs that significantly affect the overall survival (OS) of patients as OS-related genes (included lncRNAs, mRNAs, and miRNAs). Enrichment analysis and protein-protein interaction (PPI) network construction were performed for the OS-related mRNAs. We further established a ceRNAs regulatory network. In addition, the potential prognostic role of genes was further evaluated by risk score. We have identified 5275 lncRNAs, 176 miRNAs, and 6221 mRNAs that significantly affect the prognosis of pediatric AML patients. It is worth noting that OS-related mRNAs are mainly involved in ribosome, RNA transport, and spliceosome. We identified the top 10 most connected mRNAs in the PPI network as important mRNAs and constructed a ceRNAs regulatory network (including NCBP2, RPLP0, UBC, RPS2, and RPS9). The risk score and nomogram results suggest that NCBP2 may be a risk factor for pediatric AML, while RPLP0, UBC, RPS2, and RPS9 may be protective factors. Our results construct 5 gene signals as new prognostic indicators for predicting the survival of pediatric AML patients. Our research has demonstrated the ceRNAs regulatory network may become a new target for pediatric AML treatment.
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