Identification of crucial genes and prediction of small molecules for multidrug resistance of Hodgkin’s lymphomas

Article type: Research Article

Authors: Huang, Yi^{a; 1; *} | Huang, Yu^{b; 1} | Zhang, Liang^c | Chang, Aoshuang^d | Zhao, Peng^a | Chai, Xiao^a | Wang, Jishi^{a; *}

Affiliations: [a] Department of Internal Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China | [b] Department of Invasive Technology, Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, China | [c] Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China | [d] School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, China

Correspondence: [*] Corresponding authors: Yi Huang, Jishi Wang, Department of Internal Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. E-mail: huangyigy@126.com;wangjishi9646@163.com.

Note: [1] Yi Huang and Yu Huang contributed equally to this work.

Abstract: BACKGROUND: Multidrug resistance of Hodgkin’s lymphoma (HL) often results in recurrence. Thus, we aimed to explore the underlying molecular mechanisms of multidrug resistance using bioinformatics strategies. METHODS: The gene expression profile was obtained from GEO database. Then, the differentially expressed genes were screened out, and their functional annotations were carried out. Then, gene-signal interaction network was constructed and Connectivity Map (CMAP) analysis was performed. RESULTS: A total of 1425 dysregulated genes were screened out, which were mainly enriched in biological items, such as small molecule metabolic, signal transduction, and cell apoptosis. Some survival-related pathways, such as MAPK pathways, apoptosis, and P53 pathway, and several hub genes, such as PRKCA, ACTN1, PIP5K1B, PRKACB, and JAK2, might play key roles in the development of multidrug resistance. Interestingly, felodipine was predicted to be a potential agent overcoming the multidrug resistance. CONCLUSIONS: The present study offered new insights into the molecular mechanisms of multidrug resistance and identified a series of important hub genes and small agents that might be critical for treatment of multidrug-resistant HL.

Keywords: Multidrug resistance, differentially expressed genes, dysfunctional pathway, function enrichment analysis, Hodgkin’s lymphoma

DOI: 10.3233/CBM-181496

Journal: Cancer Biomarkers, vol. 23, no. 4, pp. 495-503, 2018