Identification of Hub Genes Associated with Resistance to Prednisolone in Acute Lymphoblastic Leukemia Based on Weighted Gene Co-expression Network Analysis

Abstract

Resistance against glucocorticoids which are used to reduce inflammation and treatment of a number of diseases, including leukemia, is known as the first stage of treatment failure in acute lymphoblastic leukemia. Since these drugs are the essential components of chemotherapy regimens for ALL and play an important role in stop of cell growth and induction of apoptosis, it is important to identify genes and the molecular mechanism that may affect glucocorticoid resistance. In this study, we used the GSE66705 dataset and weighted gene co-expression network analysis (WGCNA) to identify modules that correlated more strongly with prednisolone resistance in type B lymphoblastic leukemia patients. The PPI network was built using the DEGs key modules and the STRING database. Finally, we used the overlapping data to identify hub genes. out of a total of 12 identified modules by WGCNA, the blue module was find to have the most statistically significant correlation with prednisolone resistance and Nine genes including SOD1, CD82, FLT3, GART, HPRT1, ITSN1, TIAM1, MRPS6, MYC were recognized as hub genes Whose expression changes can be associated with prednisolone resistance. Enrichment analysis based on the MsigDB repository showed that the altered expressed genes of the blue module were mainly enriched in IL2_STAT5, KRAS, MTORC1, and IL6-JAK-STAT3 pathways, and their expression changes can be related to cell proliferation and survival. The analysis performed by the WGCNA method introduced new genes. The role of some of these genes was previously reported in the resistance to chemotherapy in other diseases. This can be used as clues to detect treatment-resistant (drug-resistant) cases in the early stages of diseases.

Keywords: Acute lymphoblastic leukemia; Glucocorticoid resistance; Hub genes; WGCNA.