Identifying Key Genes, miRNAs, and lncRNAs in Lennert Lymphoma Through Comprehensive Network Analysis of Diverse Omics Data

Lennert lymphoma (LL) is a rare subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). This malignancy originates from T cells, which play a fundamental role in the immune system. Under normal conditions, T cells are responsible for protecting against malignancies; however, in this disease, they become malignant. This transformation creates a tumor-suppressive microenvironment, which can compromise immune function and promote tumor progression. This phenomenon underscores the dual role of T cells in pathogenesis. LL accounts for approximately ۶% of non-Hodgkin lymphomas and is associated with an unfavorable prognosis, with a median overall survival of about ۱۶ months (Patsouris et al., ۱۹۹۳). Consequently, understanding these dynamics is crucial for developing therapies aimed at enhancing or restoring the protective functions of the immune system. In this work, data from ۱۰ normal samples and ۱۲ patient samples retrieved from the GEO database (GSE۱۳۲۵۵۰) were analyzed to identify key biomarkers associated with Lennert lymphoma (Etebari et al., ۲۰۱۹). The analysis identified ۴۰۵ genes with adjusted adj.P.Val<۰.۰۰۱ and |logFC|>۸. Initially, a protein-protein interaction network for these genes was generated using the STRING database. From this network, ۱۰ genes with the highest degree centrality FN۱, VWF, MMP۹, APOE, DCN, COL۱A۲, BGN, COL۳A۱, CXCL۱۲, and LUM were identified as key hub genes. Next, miRNAs associated with these proteins were extracted from the mirDB database, and their corresponding lncRNAs were identified using the LncTarD database and a lncRNA-mRNA-miRNA network was constructed. This process resulted in the construction of a lncRNA-mRNA-miRNA triad network comprising ۵۵۷ unique vertices and ۱,۲۴۴ edges. In the analysis of this network, miRNAs and lncRNAs with the strongest relationships to the hub proteins were identified as key biomarkers. These included microRNAs such as hsa-miR-۶۰۷ (associated with DCN, FN۱, and COL۱A۲) and hsa-miR-۲۹۸ (associated with DCN, FN۱, and COL۱A۲); hsa-miR-۱۵۳-۵p (associated with COL۱A۲, COL۳A۱, and FN۱); hsa-miR-۳۱۶۳ (associated with LUM, COL۳A۱, and FN۱); and hsa-miR-۴۵۰۰ (associated with DCN, COL۳A۱, and COL۱A۲). Additionally, three lncRNAs AOC۴P (associated with COL۱A۲ and MMP۹), FENDRR (associated with FN۱ and MMP۹), and NEAT۱ (associated with FN۱ and MMP۹) were identified

کلیدواژه ها:

Lennert Lymphoma ، miRNAs ، lncRNAs ، network analysis ، omics data