همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Simultaneous overexpression of CD70 and downregulation of CD84 as a prognostic marker for glucocorticoid resistance in B cell Acute lymphoblastic leukemia

نویسندگان :

Mohammad Hossein Shakib Manesh¹ Soheila Rahgozar²

1- دانشگاه اصفهان 2- دانشگاه اصفهان

کلمات کلیدی :

Drug resistance،Glucocorticoids،Acute Lymphoblastic Leukemia،Transcriptomics،Prognostic marker

چکیده :

Acute lymphoblastic leukemia (ALL) is a type of blood cancer originating from lymphocytes of the immune system that spreads rapidly (Gokbuget and Boissel, 2024). ALL is one of the most common cancers in children with an increasing annual rate, although it also occurs in adults (Katebi and Rahgozar, 2023). Based on origin, this cancer is classified into B and T-ALL, with the B type being more common (Brown and Shah, 2021). Glucocorticoids, particularly Prednisolone and Dexamethasone, are highly valuable in the treatment of ALL (Pourhassan and Murphy, 2024). This importance is primarily due to their ability to induce apoptosis in cancer cells through glucocorticoid receptor activation (Inaba and Pui, 2010). However, cancer cell resistance often disrupts their effectiveness (Bergeron and Barnett, 2023). Studying the causes and patterns of drug resistance can aid in accelerating the replacement of treatment protocols and combating this phenomenon (Abdoul-Azize and Hami, 2024). In this study, transcriptomics data were used to compare gene expression levels in glucocorticoid-resistant and sensitive cell lines. Microarray and RNAseq transcriptome data related to glucocorticoid-resistant and sensitive B-ALL cell lines were extracted from the GEO database with accession numbers GSE94302, GSE217428, and GSE214319 (Sarno and Domizi, 2023; Sbirkov and Vergov, 2023). Data analysis was performed using the R and Galaxy (Galaxy, 2024) platforms for microarray and RNAseq data, respectively. DEG analysis was conducted between resistant and sensitive groups for each dataset (Law and Chen, 2014; Phipson and Lee., 2016). Genes with significant expression level changes (Adj.P.Val<0.05, |logFC|>1) in each dataset were extracted and ultimately intersected among all three datasets. Among the final genes, CD70 and CD84 showed significant increases and decreases in expression in resistant cells, respectively. Gene ontology enrichment analysis related to CD70 and CD84 was performed using the String database (Szklarczyk and Kirsch, 2023) and Cytoscape application (Shannon and Markiel, 2003). Although both CD70 and CD84 have a role in activating immune cells, the reason why resistant cancer cells overexpress CD70 is a controversial issue. Based on literature reviews exceeded expression of CD70 can exhaust T cells instead of activating them (Nie and Ren, 2022). In this study, simultaneous overexpression of CD70 and downregulation of CD84 in B-ALL was introduced as a prognostic marker for drug resistance to glucocorticoids. This study can help identify more effective treatment options for B-ALL patients who are resistant to glucocorticoids.