AUTHOR=Xu Cong , Liang Ting , Liu Jing , Fu Yunfeng 

TITLE=RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.931501

DOI=10.3389/fphar.2022.931501

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis.</p><p><bold>Methods:</bold> RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein–protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database.</p><p><bold>Results:</bold> RAB39B was highly expressed in multiple tumors including DLBCL. The protein–protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine–cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4<sup>+</sup> T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. <italic>In vitro</italic> experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells.</p><p><bold>Conclusion:</bold> RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.</p>