Abstract
The incidence of chronic myeloid leukemia (CML) is increasing year by year, which is a serious threat to human health. Early diagnosis can reduce mortality and improve prognosis. LncRNAs have been shown to be effective biomarkers for a variety of diseases and can act as competitive endogenous RNA (ceRNA). In this study, the dysregulated lncRNA-associated ceRNA networks (DLCN) of the chronic phase (CP), accelerated phase (AP), and blastic crisis (BC) for CML are constructed. Then, based on dynamic network biomarkers (DNB), some dysregulated lncRNA-associated ceRNA network biomarkers of CP, AP, and BC for CML are identified according to DNB criteria. Thus, a lncRNA (SNHG5) is identified from DLCN_CP, a lncRNA (DLEU2) is identified from DLCN_AP, and two lncRNAs (SNHG3, SNHG5) are identified from DLCN_BC. In addition, the critical index (CI) used to detect disease outbreaks shows that CML occurs in CP, which is consistent with clinical medicine. By analyzing the functions of the identified ceRNA network biomarkers, it has been found that they are effective lncRNA biomarkers directly or indirectly related to CML. The result of this study will help deepen the understanding of CML pathology from the perspective of ceRNA and help discover the effective biomarkers of CP, AP, and BC for CML in the future, so as to help patients get timely treatment and reduce the mortality of CML.
Highlights
Chronic myeloid leukemia (CML) is a clonal malignant proliferative disease of hematopoietic stem cells (HSCs). e main hallmark is the formation of BCR-ABL fusion gene at the molecular level [1]
The critical index (CI) constructed to detect disease outbreaks shows that CML occurs in chronic phase (CP), which is consistent with clinical medicine. en, functional enrichment analysis is performed on the identified competitive endogenous RNA (ceRNA) network biomarkers, and the role of the 3 lncRNAs in CML is validated by KEGG enrichment analysis and literature mining. ese novel lncRNAs acting as ceRNAs at the posttranscriptional level may become promising diagnostic biomarkers and therapeutic targets
To further investigate the competition between mRNA and lncRNA in CP, acceleration phase (AP), and blast crisis (BC) of CML, dynamic network biomarkers (DNB) is used to screen a module in the dysregulated lncRNA-associated ceRNA networks, and identify the lncRNA-associated ceRNA network biomarkers for CML
Summary
Chronic myeloid leukemia (CML) is a clonal malignant proliferative disease of hematopoietic stem cells (HSCs). e main hallmark is the formation of BCR-ABL fusion gene at the molecular level [1]. E main hallmark is the formation of BCR-ABL fusion gene at the molecular level [1]. E resultant protein-tyrosine kinase (PTK) drives signaling events and transforms HSCs. BCR-ABL activity in HSC causes CML [2]. CML presents in the chronic phase (CP), and it will invariably transform through the acceleration phase (AP) without curative intervention, progression proceeds to blast crisis (BC). Patients generally die of infection and bleeding complications due to a lack of normal granulocytes and platelets [2]. The BCR-ABL fusion gene has been determined as a pathogenic gene of CML, it is only used for the diagnosis of CML and does not reflect the molecular mechanism and three stages of CML
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