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

Abstract

Background: Acute Myeloid Leukemia (AML) is a complex and heterogeneous hematologic malignancy. However, the function of prognosis-related signature genes in AML remains unclear.Methods: 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.Results: 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 CCL5 and lncRNA UCA1 was a significant impact on the prognosis of AML. Besides, we found three potential interactions networks such as lncRNA UCA1/hsa-miR-16-5p/COL4A5, lncRNA UCA1/hsa-miR-16-5p/SPARC, and lncRNA SNORA27/hsa-miR-17-5p/CCL5 may play an important role in AML. Furthermore, the evaluation of the immune infiltration shows that CCL5 is positively correlated with various immune signatures, and lncRNA UCA1 is negatively correlated with the immune signatures. Finally, the result of qRT-PCR showed that CCL5 is down-regulated and lncRNA UCA1 is up-regulated in AML samples separately.Conclusions: In conclusion, we propose that CCL5 and lncRNA UCA1 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.

Comprehensive analysis of cuproptosis-associated LncRNAs predictive value and related CeRNA network in acute myeloid leukemia

“…Due to the lack of corresponding miRNA expression data in the TCGA-LAML and GTEx datasets, we searched PubMed for studies on these miRNAs in AML. From previous literature, the expression of miR-93-5p [ 26 , 27 ], miR-124-3p [ 28 , 29 ], miR-185-5p [ 30 , 31 ], miR-20a-5p [ 32 , 33 ], and miR-17-5p [ 34 , 35 ] differs in AML patients compared to healthy controls. Meanwhile, miR-106a-5p was consistently overexpressed in settings where AML was resistant to therapy.…”

The Role of CXCR1, CXCR2, CXCR3, CXCR5, and CXCR6 Ligands in Molecular Cancer Processes and Clinical Aspects of Acute Myeloid Leukemia (AML)

“…According to the GEPIA portal (http://gepia.cancer-pku.cn, accessed on 10 July 2023), higher expression of CXCL3, CXCL5, and PPBP in AML cells is associated with poorer prognoses for patients with the described leukemia [9,52]. Other bioinformatic analyses also confirmed that higher CXCL5 expression in AML cells is related to poorer prognoses [57]. According to the UALCAN portal (https://ualcan.path.uab.edu, accessed on 10 July 2023), there is a tendency (p = 0.093) for poorer prognoses with higher PPBP expression in AML cells [8,10].…”

“…The level of CXCR6 expression in the blood of AML patients may be associated with better outcomes [ 57 ], but conflicting results have been reported [ 51 ].…”

Akut ve Kronik Miyeloid Lösemili Hastalarda Prognostik miRNA İmzasının Biyoinformatik Analiz ile Karşılaştırılması

“…As a result, they can be used as diagnostic, prognostic, and therapeutic biomarkers at various stages of leukemia. Furthermore, growing evidence suggests that miRNAs could be used as markers in diagnosis and treatment in the early stages of the disease or following chemotherapy (21,22).…”