Analysis of the differential expression and prognostic relationship of DEGs in AML based on TCGA database

Abstract:Background: Acute myeloid leukemia (AML) is a common and lethal haematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates.Methods: The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we 1) screened the survival related DEGs by Cox regression analysis, 2) selected the cytogenetics risk related DEGs by DESeq2 R package, 3) and filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of our present study. The following Multivariate Cox regression analyses were performed to analyze these intersectional genes as independent factors. Proportional hazards assumption was evaluated to test Cox regression model by Schoenfeld residuals. The Kaplan–Meier survival curve and Nomogram were plotted to predict and compare the 1-year, 3-year, and 5-year survival rates of AML patients. The concordance index (C-index) and calibration curve were used to evaluate the prediction performance of nomogram.Results: A total of 151 RNA-Seq samples for 60488 genes and 200 clinical samples were selected from the TCGA database. 1005 survival related DEGs were obtained by Cox regression analyses (P1), 2291 cytogenetics risk category related DEGs were identified using DESeq2 (log₂ Fold Change>1 and P<0.05), and 790 meaningful pathways of cytogenetics risk category were selected from GSEA (abs(NES)≥1, NOM p-val≤0.05 and FDR q-val≤0.25). Screened a key gene IGHM that is related to patient survival rate. The results showed that the IGHM expression and age displayed statistical associations with the survival time of patients (P<0.05). The risk of death in the patients with high expression group of IGHM was 2.07 times higher than those in low expression group (P<0.05). For survival, the 1, 3, and 5-year survival of patients in the high expression group are predicted to be 68%, 43%, and 30%. GSEA analysis revealed that IGHM were mainly enriched in the immune response (BP).Conclusion: High expression of IHGM gene is an independent risk factor for the prognosis of patients with AML and can be an important molecular marker for predicting the prognosis of patients with AML.