ABSTRACT
INTRODUCTION: The aim of the study was to construct a pyroptosis-related risk score (RS) model for the prognosis of acute myeloid leukemia (AML). METHODS: The TARGET (training) and E-MTAB-1216 (validation) datasets were downloaded. Pyroptosis-related genes with differences in expression were identified between the recurrent and nonrecurrent samples of the training dataset. An RS prognostic model comprising seven pyroptosis-related genes was constructed using LASSO regression coefficients. The samples were classified into the high- and low-risk groups using the RS model; the differentially expressed genes (DEGs) between these groups were identified, followed by DEG functional analysis and the immunological evaluation of these groups. RESULTS: Forty-nine pyroptosis-related genes, including 22 DEGs, were screened. WT1, NPM, FLT3/ITD, and CEBPA mutations were found in most pediatric AML samples. An RS prognostic model was constructed using 7 pyroptosis-related genes. The two risk groups and prognostic data were significantly related. FLT3/ITD mutations, CEBPA mutations, and RS model status were identified as independent prognostic factors, using the clinical information. The DEGs between the two groups were correlated with immune-related pathways. Moreover, the immune cell distribution and the occurrence of immune-related pathways were notably decreased in the high-risk group. DISCUSSION/CONCLUSION: Seven pyroptosis-related genes, CHMP2A, PRKACA, CASP9, IRF2, CHMP3, HMGB1, and AIM2, can predict the prognosis and recurrence of childhood AML.
Subject(s)
Leukemia, Myeloid, Acute , Pyroptosis , Child , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/epidemiology , Mutation , Prognosis , Pyroptosis/genetics , Risk FactorsABSTRACT
The roles of microRNA (miRNA/miR)-383-5p have been reported in several malignancies, including breast cancer, gastric cancer, ovarian cancer and lung adenocarcinoma. However, its function in diffuse large B-cell lymphoma (DLBCL) remains unclear. Thus, the present study aimed to investigate the role of miR-383-5p in DLCBL. Reverse transcription-quantitative PCR analysis was performed to detect miR-383-5p expression in 80 paired tissue samples from patients with DLBCL and control subjects, as well as related cancer cell lines. Kaplan-Meier survival analysis was performed, and the prognostic value of miR-383-5p was determined via Cox regression analysis. Furthermore, the association between miR-383-5p expression and the clinicopathological characteristics of patients with DLBCL was investigated. The Cell Counting Kit-8, crystal violet staining and Transwell assays were performed to assess the effects of miR-383-5p on cell proliferation and invasion, respectively. The results demonstrated that miR-383-5p expression was upregulated in human DLBCL tissues and cell lines. In addition, miR-383-5p expression was closely associated with clinical stage and extranodal invasion in patients with DLBCL. Notably, high miR-383-5p expression was able to predict a favorable clinical prognosis in patients with DLBCL. Furthermore, overexpression of miR-383-5p significantly inhibited the proliferation and invasion of DLBCL cells, the effects of which were reversed following miR-383-5p knockdown. Taken together, the results of the present study suggest that miR-383-5p may predict favorable prognosis, and thus may be used as a prognostic biomarker for patients with DLBCL. In addition, miR-383-5p appears to play critical roles in inhibiting the proliferation and invasion of DLBCL cells, and thus may be used as a potential therapeutic target in patients with DLBCL.
