High Expression of the SH3TC2-DT/SH3TC2 Gene Pair Associated With FLT3 Mutation and Poor Survival in Acute Myeloid Leukemia: An Integrated TCGA Analysis

Abstract

Fms-like tyrosine kinase 3 (FLT3) mutation is one of the most common mutations in acute myeloid leukemia (AML). However, the effect of FLT3 mutation on survival is currently still controversial and the leukemogenic mechanisms are still under further investigation. The aim of our study is to identify differentially expressed genes (DEGs) in FLT3-mutant AML and to find crucial DEGs whose expression level is related to prognosis for further analysis. By mining the TCGA-LAML dataset, 619 differentially expressed lncRNAs (DElncRNAs) and 1,428 differentially expressed mRNAs (DEmRNAs) were identified between FLT3-mutant and FLT3-wildtype samples. Through weighted gene correlation network analysis (WGCNA) and the following Cox proportional hazards regression analysis, we constructed the prognostic risk models to identify the hub DElncRNAs and DEmRNAs associated with AML prognosis. The presence of both SH3TC2 divergent transcript (SH3TC2-DT) and SH3TC2 in respective prognostic risk models promotes us to further study the significance of this gene pair in AML. SH3TC2-DT and SH3TC2 were identified to be coordinately high expressed in FLT3-mutant AML samples. High expression of this gene pair was associated with poor survival. Using logistic regression analysis, we found that high SH3TC2-DT/SH3TC2 expression was associated with FLT3 mutation, high WBC count, and intermediate cytogenetic and molecular-genetic risk. AML with SH3TC2-DT/SH3TC2 high expression showed enrichment of transcripts associated with stemness, quiescence, and leukemogenesis. Our study suggests that the SH3TC2-DT/SH3TC2 gene pair may be a possible biomarker to further optimize AML prognosis and may function in stemness or quiescence of FLT3-mutant leukemic stem cells (LSCs).

A Prognostic Nomogram Combining Gene Expression Profiles and TNM Stage Predicts Survival in Gastric Cancer

“…As interest in personalized medicine has grown, a few prognostic risk classi ers have been identi ed and found to enhance survival predictions in a variety of cancers [29][30][31][32][33][34][35] . However, most of these studies have focused only on statistical power in the screening of molecular markers, without regard for their clinical signi cance, in our study, we combined the TNM stage with molecular pro ling.…”

Aberrant Bone Homeostasis in AML Is Associated with Activated Oncogenic FLT3-Dependent Cytokine Networks

“…Oncogenic FLT3 ITD mutations commonly found in AML patients have a great impact on gene expression. Aberrant gene expression in FLT3 ITD-positive AML patients is a known feature of this disease [3,[46][47][48]. The molecular mechanisms of how oncogenic mutant FLT3 controls aberrant leukaemogenesis have been frequently addressed (for a recent review, see [3]).…”

Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance

“…LONG NONCODING RNAs ASSOCIATED FLT3-INTERNAL TANDEM DUPLICATION, TET2, AND DNMT3A MUTATIONS About 30% of AML cases have mutations in the Fmslike tyrosine kinase 3 (FLT3) gene. The more frequent ITD mutation in the juxtamembrane domain is found in 25% of AML cases whereas point mutation or deletion in the tyrosine kinase domain (TKD) is found in about 7-10% of AML cases [40]. Also, the genes involved in DNA methylation including teneleven translocation 2 (TET2) and DNA methyltransferase 3A (DNMT3A) are frequently mutated in CN-AML patients [41].…”