Comprehensive bioinformatic analysis of the expression and prognostic significance of TSC22D domain family genes in adult acute myeloid leukemia

Abstract

Background TSC22D domain family genes, including TSC22D1-4, play a principal role in cancer progression. However, their expression profiles and prognostic significance in adult acute myeloid leukemia (AML) remain unknown. Methods The online databases, including HPA, CCLE, EMBL-EBI, GEPIA2, BloodSpot, GENT2, UCSCXenaShiny, GSCALite, cBioportal, and GenomicScape, utilized the data of TCGA and GEO to investigate gene expression, mutation, copy number variation (CNV), and prognostic significance of the TSC22D domain family in adult AML. Computational analysis of resistance (CARE) was used to explore the effect of TSC22D3 expression on drug response. Functional enrichment analysis of TSC22D3 was performed in the TRRUST Version 2 database. The STRING, Pathway Commons, and AnimalTFDB3.0 databases were used to investigate the protein–protein interaction (PPI) network of TSC22D3. Harmonizome was used to predict target genes and kinases regulated by TSC22D3. The StarBase v2.0 and CancermiRNome databases were used to predict miRNAs regulated by TSC22D3. UCSCXenaShiny was used to investigate the correlation between TSC22D3 expression and immune infiltration. Results Compared with normal adult hematopoietic stem cells (HSCs), the expression of TSC22D3 and TSC22D4 in adult AML tissues was markedly up-regulated, whereas TSC22D1 expression was markedly down-regulated. The expression of TSC22D1 and TSC22D3 was significantly increased in adult AML tissues compared to normal adult tissues. High TSC22D3 expression was significantly associated with poor overall survival (OS) and event-free survival (EFS) in adult AML patients. Univariate and multivariate Cox analysis showed that overexpression of TSC22D3 was independently associated with adverse OS of adult AML patients. High TSC22D3 expression had a adverse impact on OS and EFS of adult AML patients in the chemotherapy group. TSC22D3 expression correlated with drug resistance to BCL2 inhibitors. Functional enrichment analysis indicated that TSC22D3 might promote AML progression. MIR143-3p sponging TSC22D3 might have anti-leukemia effect in adult AML. Conclusions A significant increase in TSC22D3 expression was observed in adult AML tissues compared to normal adult HSCs and tissues. The prognosis of adult AML patients with high TSC22D3 expression was unfavorable, which could severe as a new prognostic biomarker and potential target for adult AML.

Effective Prognostic Model for Therapy Response Prediction in Acute Myeloid Leukemia Patients

“…In the last few years, a lot of information, based mainly on the computational approach concerning the predictive role of individual genetic and molecular markers for leukemia patients resistant to chemotherapy, has appeared. For example, in the study of Xu et al, tight associations between the high expression of TSC22D3 domain family genes playing an essential role in tumor progression with poor overall and event-free survival and drug resistance to BCL2 inhibitors in adult AML patients, especially in the chemotherapy group, have been reported [ 47 ]. The study of Liu et al demonstrated that high miR-107 or miR-17 expression levels were associated with poorer overall survival and event-free survival in the chemotherapy cohort of patients with de novo AML [ 48 ].…”

Exploring the Immune-Related Senescence biomarkers in Predicting Gestational Diabetes Mellitus

“…The expression data of 1267 transcription factors (TFs) in humans were obtained from the AnimalTFDB3.0 database (http://bioinfo.life.hust.edu.cn/AnimalTFDB#!) [26]. The Pearson correlation coefficient between TFs and biomarkers was computed by the R package "psych" (version 2.1.9).…”