Identification of Myelodysplastic Syndrome Risk-related Genes and their Association with Immune Infiltration

Abstract

Abstract Objective Myelodysplastic syndrome (MDS) is a hematological malignancy. Recently, immune cells participate in the occurrence and progression of various tumors has revealed by many researches. In this study, we investigated the correlation between the expression levels of MDS risk-related genes and the ratio of tumor-infiltrating immune cells in CD34+ cells. Our research may provide some help for the basis of the pathogenesis of MDS and the prognosis analysis of patients. Methods This research was based on two microarray datasets GSE19429 and GSE58831. The differential expressed genes (DEGs) of low risk vs. high risk MDS were analyzed by GEO2R. The GO and KEGG pathways of DEGs were identified by enrichment analysis. Three risk-related genes were screened and identified by LASSO analysis and MCC algorithm. Then, the tumor immune cell infiltration of CD34+ cells in MDS patients were analyzed by CIBERSORT to define the differences in tumor immune cell infiltration between low-risk and high-risk MDS. Results We collected 179 transcriptomes and 159 transcriptomes from dataset GSE58831and GSE19429. We found that low-risk and high-risk MDS patients had significant differences in prognosis. Besides, 105 common DEGs was identified in both datasets, which were mainly enriched in malaria, African trypanosomiasis, transcriptional dysregulation in cancer, phagosome, and primary immunodeficiency in the KEGG pathway. Three risk-related genes were screened by LASSO analysis and MCC algorithm: CDC6, RRM2, HMMR. There was a significant difference in the prognosis between the high-risk group and the low-risk group differentiated by these 3 gene markers. In addition, Treg, mast cells, CD8+ T cells, Macrophage M2, Eosinophils and Neutrophils were also found significantly difference between low-risk and high-risk MDS in tumor immune cell infiltration (P < 0.05). Also, three risk-related genes and tumor immune cells were significantly correlated. Conclusion We screened out three risk-related genes in MDS. CDC6, HMMR and RRM2 are highly expressed in the low-risk group of MDS and low in the high-risk group, and the expression levels of the three genes are closely related to the infiltration of various immune cells. This conclusion has potential clinical prognostic value for MDS patients.