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INTERNATIONAL CONGRESS OF

CancerGenetics

• Integrative Bioinformatics Analysis Identifies FYN and Its lncRNA–miRNA Network as Prognostic Biomarkers in Acute Myeloid Leukemia

• Pegah Bozorgzad Moghim,^1,* Maryam Sadat Sajadi Javan,² Arsham Azari Dehkordi,³ Shiva Vaheb Hosseinabadi,⁴ Mansoureh Azadeh,⁵
  1. Zist Fanavari Novin Biotechnology Institute
  2. Zist Fanavari Novin Biotechnology Institute
  3. Zist Fanavari Novin Biotechnology Institute
  4. Zist Fanavari Novin Biotechnology Institute
  5. Zist Fanavari Novin Biotechnology Institute
  
  
  
• Introduction: Acute myeloid leukemia (AML) is an aggressively advancing myeloid disorder identified with the clonal proliferation of primitive hematopoietic progenitor cells, referred to as blasts, in the bone marrow. This expansion leads to ineffective erythropoiesis and megakaryopoiesis, clinically presenting as a relatively rapid onset of bone marrow failure compared to chronic and indolent leukemias. Long noncoding RNAS (lncRNA) are a class of transcripts longer than 200 nucleotides (nt) typically lack protein-coding potential. LncRNAS have been shown to play a vital role in regulating multiple aspects of tumor development and progression, including cell proliferation, metastasis, metabolism, and therapy resistance. The study aims to identify biomarkers with the use of various bioinformatics analyses.
• Methods: Microarray analysis was conducted on dataset GSE90062 related to Acute myeloid leukemia cancer from the GEO database. Following GEO2R analysis, a gene with significant upregulation was identified. Gene expression of this gene performed in AML using GEPIA2 and the survival analyses was checked in both GEPIA2 and ENCORI. The signaling pathways involving the selected gene were investigated through KEGG. Protein–protein interactions were analyzed using STRING. Subsequently, miRNAs targeting the gene were retrieved from TargetScan and miRTarBase, and their common candidates were identified with Cytoscape. Finally, lncRNAs associated with these shared miRNAs were obtained from LncBase (DIANA), and overlapping lncRNAs were determined using Cytoscape.
• Results: The gene FYN (LogFC =2.35, adj p-value = 0.000000110) was identified as an upregulated gene in AML in dataset GSE90062. Consistently, dot plot analysis showed a marked overexpression of FYN in AMl myeloid leukemia. Survival analysis further revealed that elevated expression of FYN is significantly associated with reduced overall survival. Furthermore, two lncRNAs (AL35505.4 and XLOC-014209), identified through miRNA-related databases, were recognized as potential biomarkers associated with AML."
• Conclusion: In this study, FYN was identified as a potential biomarker in acute myeloid leukemia (AML), with its high expression associated with reduced patient survival. Pathway analysis revealed that FYN participates in key processes such as PI3K–Akt signaling, focal adhesion, and osteoclast differentiation, suggesting its role in leukemic blast expansion and resistance to apoptosis. Furthermore, two novel lncRNAs (AL35505.4 and XLOC-014209) were introduced as potential upstream regulators of FYN through interactions with miRNAs, which have not previously been reported in AML. These findings indicate that the lncRNA–miRNA–FYN axis may play an important role in AML pathogenesis; however, further experimental and clinical studies are required for definitive validation.
• Keywords: 1.Acute Myeloid Leukemia (AML) 2. FYN 3. Long noncoding RNA (lncRNA) 4. Biomarker 5. PI3K–Akt signal