AUTHOR=Wang Jie , Uddin Md. Nazim , Hao Jian-ping , Chen Rong , Xiang Yun-xia , Xiong Dai-qin , Wu Yun 

TITLE=Identification of Potential Novel Prognosis-Related Genes Through Transcriptome Sequencing, Bioinformatics Analysis, and Clinical Validation in Acute Myeloid Leukemia

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.723001

DOI=10.3389/fgene.2021.723001

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Acute Myeloid Leukemia (AML) is a complex and heterogeneous hematologic malignancy. However, the function of prognosis-related signature genes in AML remains unclear.</p><p><bold>Methods:</bold> In the current study, transcriptome sequencing was performed on 15 clinical samples, differentially expressed RNAs were identified using R software. The potential interactions network was constructed by using the common genes between target genes of differentially expressed miRNAs with transcriptome sequencing results. Functional and pathway enrichment analysis was performed to identify candidate gene-mediated aberrant signaling pathways. Hub genes were identified by the cytohubba plugin in Cytoscape software, which then expanded the potential interactions regulatory module for hub genes. TCGA-LAML clinical data were used for the prognostic analysis of the hub genes in the regulatory network, and GVSA analysis was used to identify the immune signature of prognosis-related hub genes. qRT-PCR was used to verify the expression of hub genes in independent clinical samples.</p><p><bold>Results:</bold> We obtained 1,610 differentially expressed lncRNAs, 233 differentially expressed miRNAs, and 2,217 differentially expressed mRNAs from transcriptome sequencing. The potential interactions network is constructed by 12 lncRNAs, 25 miRNAs, and 692 mRNAs. Subsequently, a sub-network including 15 miRNAs as well as 12 lncRNAs was created based on the expanded regulatory modules of 25 key genes. The prognostic analysis results show that <italic>CCL5</italic> and lncRNA <italic>UCA1</italic> was a significant impact on the prognosis of AML. Besides, we found three potential interactions networks such as lncRNA <italic>UCA1</italic>/hsa-miR-16-5p/<italic>COL4A5</italic>, lncRNA <italic>UCA1</italic>/hsa-miR-16-5p/<italic>SPARC</italic>, and lncRNA <italic>SNORA27</italic>/hsa-miR-17-5p/<italic>CCL5</italic> may play an important role in AML. Furthermore, the evaluation of the immune infiltration shows that <italic>CCL5</italic> is positively correlated with various immune signatures, and lncRNA <italic>UCA1</italic> is negatively correlated with the immune signatures. Finally, the result of qRT-PCR showed that <italic>CCL5</italic> is down-regulated and lncRNA <italic>UCA1</italic> is up-regulated in AML samples separately.</p><p><bold>Conclusions:</bold> In conclusion, we propose that <italic>CCL5</italic> and lncRNA <italic>UCA1</italic> could be recognized biomarkers for predicting survival prognosis based on constructing competing endogenous RNAs in AML, which will provide us novel insight into developing novel prognostic, diagnostic, and therapeutic for AML.</p>