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Identification of Hub Genes Associated with Resistance to Prednisolone in Acute Lymphoblastic Leukemia Based on
Shahram Nekoeian1,2, Shaghayegh Ferdowsian2, Yazdan Asgari3
1Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, No. 88, School of Advanced Technologies in Medicine, Italia st, Keshavarz Blvd, Tehran, 1417755469, Iran.
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.
Insights
Glucocorticoid resistance in acute lymphoblastic leukemia (ALL) is a major treatment challenge. This study identified nine hub genes and key molecular pathways, including IL2-STAT5 and IL6-JAK-STAT3, associated with prednisolone resistance in ALL patients.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Glucocorticoids are crucial in acute lymphoblastic leukemia (ALL) chemotherapy, targeting cell growth and apoptosis.
- Resistance to glucocorticoids represents the primary treatment failure in ALL.
- Identifying molecular mechanisms underlying glucocorticoid resistance is essential for improving ALL treatment outcomes.
Purpose of the Study:
- To identify genes and molecular pathways associated with prednisolone resistance in acute lymphoblastic leukemia (ALL).
- To explore potential biomarkers for early detection of treatment-resistant ALL.
Main Methods:
- Weighted Gene Co-expression Network Analysis (WGCNA) applied to the GSE66705 dataset.
- Construction of a Protein-Protein Interaction (PPI) network using differentially expressed genes (DEGs) from key modules.
- Identification of hub genes through overlapping data analysis and enrichment analysis using the MsigDB repository.
Main Results:
- The blue module identified by WGCNA showed the strongest correlation with prednisolone resistance.
- Nine hub genes, including SOD1, CD82, FLT3, GART, HPRT1, ITSN1, TIAM1, MRPS6, and MYC, were identified.
- Enriched pathways associated with the blue module include IL2-STAT5, KRAS, MTORC1, and IL6-JAK-STAT3, linked to cell proliferation and survival.
Conclusions:
- This study identified novel genes and pathways implicated in glucocorticoid resistance in ALL.
- The identified hub genes and pathways offer potential targets for understanding and overcoming treatment resistance.
- These findings may aid in the early detection of drug-resistant ALL cases, guiding personalized treatment strategies.
