Reconstruction of Hippo Signaling Pathway Co-Expression Network in AML

Backgrounds: Acute myeloid leukemia (AML) is the prevalent form of adult leukemia withpoor overall survival (OS), increasing AML incidence. It has been shown that the Hipposignaling pathway (HSP) can influence patient survival outcomes in malignancies. Theexpression pattern of some Hippo members is also associated with predicting AML. This studycarried out a co-expression analysis to reconstruct the HSP in AML.Materials and Methods: The microarray data GSE۱۱۴۸۶۸ from GEO database was analyzed bylimma and WGCNA package in R to reconstruct the HSP in AML. The module preservationanalysis was performed to assess preserved modules, including HSP genes in the AML network.Subsequently, a protein-protein interaction (PPI) network using STRING followed by functionalenrichment analysis by ClueGO Cytoscape plug-in was done. Then, the prognostic significanceof co-expressed genes was explored in terms of overall survival by GEPIA۲.Results: Five preserved modules out of ۱۷ modules were detected through network clustering.Our results indicate the Purple preserved module containing ۷۴ members of HSP, which suggestdysregulated co-expressed AML biomarkers including cebpa, nrxn۲, cyp۴f۳, and tacstd۲ interactwith transcription factors such as gli۲, snai۲, tead۱, tead۴, tp۷۳, and wwtr۱. Moreover, our datashow some key HSP members contribute to AML, such as frmd۱, yap۱, tgfb۳, fgf۱, and wntFamily Members. ClueGO revealed the purple module was mainly enriched in adherens and tightjunction, JUN kinase activity, Wnt signaling, Hedgehog signaling, and kinase regulationpathways. Moreover, overall survival analysis confirmed the poor prognosis by HSP membersdysregulation and new suggested regulatory factors between leukemia and normal samples.Conclusion: We established the co-expression network signature correlated with genespotentially involved in AML development and the prognostic potential of the HSP. Thesefindings can further reveal the importance of HSP and novel genes contributing to AML.

کلیدواژه ها:

Acute myeloid leukemia ، Hippo signaling pathway ، Weighted gene co-expression network analysis ، Survival rate