Gene coexpression network analysis revealed biomarkers correlated with blast cells and survival in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with a poorly understood pathogenesis, especially among patients with no known cytogenetic abnormalities. Furthermore, there is a lack of therapeutic gene targets and diagnostic biomarkers for the effective treatment of AML. The present study aimed to identify candidate biomarkers correlated with the clinical prognosis of patients with AML. Leukemic cells from 5 patients with AML exhibiting a normal karyotype, and hematopoietic cells from 5 healthy donors were processed for RNA sequencing (RNA-seq), and the obtained RNA expression profiles were subjected to weighted gene correlation network analysis. A novel group of genes (the red module) were identified to be significantly associated with AML, and this module contained a closely connected network with 147 nodes, which corresponded to 114 mRNAs. Analysis of the correlation between these mRNAs and blast cell percentage, overall survival (OS) and disease-free survival (DFS) using cases from The Cancer Genome Atlas (TCGA) database revealed that CSF3R, ALPL and LMTK2 were negatively associated with the percentage of blast cells, while high expression of these genes was associated with longer OS and DFS in patients with AML. The differential expression of these three genes between patients with AML and healthy control subjects was supported using the Genotype-Tissue Expression and TCGA databases and was further confirmed using reverse transcription-quantitative (RT-qPCR). These genes exhibited significantly lower expression in patients with AML compared with control subjects. The results indicated that CSF3R, ALPL and LMTK2 exhibit the potential to be prognostic biomarkers. However, the biological functions of these three candidate genes need to be assessed in further studies.

Identification of Survival-Related Genes in Acute Myeloid Leukemia (AML) Based on Cytogenetically Normal AML Samples Using Weighted Gene Coexpression Network Analysis

“…This hypothesis has been experimentally substantiated in various types of cancers, including hematological malignancies [40][41][42][43][44]. Nowadays, there are more and more studies involving applying WGCNA in AML-related analysis published in journals of different levels [45][46][47][48][49][50], which proves the recognition of this algorithm to some extent. However, there is no study aimed at finding AML survival-specific biomarkers using the WGCNA methodology based on adult CN-AML data by far.…”

LMTK2 as Potential Biomarker for Stratification between Clinically Insignificant and Clinically Significant Prostate Cancer

“…At Definition II for csPC (Gleason score ≥ 3 + 4 and/or MCCL ≥ 4 mm), both PSA density and LMTK2 were significant prebiopsy determinants for cancer risk stratification, thus indicating that LMTK2 expression is altered at early stages of cancer progression. Despite the fact that LMTK2 expression is not specific for prostate cancer [ 37 – 39 ] due to revealed interplay between LMTK2 and myosin IV—a regulator of PSA—it is widely investigated in prostate cancer [ 40 ]. LMTK2 also interacts with other proteins, such as protein phosphatase-1 (PP1C) and inhibitor-2 (Inh2), which are involved in cell division and the cyclin-dependent kinase 5 (cdk5)/ p 35 complex, which plays important role in cell cycle progression.…”

In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia

“…Gene expression profiling of AML patients has catalyzed the discovery of novel leukemia subgroups and of prognostic signatures [6]. The increasing availability of high-throughput data from blood and bone marrow of AML patients creates unprecedented opportunities for the comprehensive identification of diagnostic biomarkers of AML which could complement and update the existing ones [15][16][17]. Moreover, despite the poor outcomes of AML, there are a few fortunate cases that manage to survive over exceptionally extended periods of time, perhaps reflecting a remarkable resistance to MRD and disease progression.…”