关键词: DBNDD1 gene expression E2F GSK-3β bioinformatic investigation cell cycle dysbindin protein family genes immunology microtubule cytoskeleton prostate cancer tumor-infiltrating immune cell

来  源:   DOI:10.3390/ijms241511930   PDF(Pubmed)

Abstract:
Prostate cancer (PCa) is one of the most prevalent cancers in men, yet its pathogenic pathways remain poorly understood. Transcriptomics and high-throughput sequencing can help uncover cancer diagnostic targets and understand biological circuits. Using prostate adenocarcinoma (PRAD) datasets of various web-based applications (GEPIA, UALCAN, cBioPortal, SR Plot, hTFtarget, Genome Browser, and MetaCore), we found that upregulated dysbindin domain-containing 1 (DBNDD1) expression in primary prostate tumors was strongly correlated with pathways involving the cell cycle, mitotic in KEGG, WIKI, and REACTOME database, and transcription factor-binding sites with the DBNDD1 gene in prostate samples. DBNDD1 gene expression was influenced by sample type, cancer stage, and promoter methylation levels of different cancers, such as PRAD, liver hepatocellular carcinoma (LIHC), and lung adenocarcinoma (LUAD). Regulation of glycogen synthase kinase (GSK)-3β in bipolar disorder and ATP/ITP/GTP/XTP/TTP/CTP/UTP metabolic pathways was closely correlated with the DBNDD1 gene and its co-expressed genes in PCa. DBNDD1 gene expression was positively associated with immune infiltration of B cells, Myeloid-derived suppressor cell (MDSC), M2 macrophages, andneutrophil, whereas negatively correlated with CD8+ T cells, T follicular helper cells, M1 macrophages, and NK cells in PCa. These findings suggest that DBNDD1 may serve as a viable prognostic marker not only for early-stage PCa but also for immunotherapies.
摘要:
前列腺癌(PCa)是男性中最常见的癌症之一,然而,其致病途径仍然知之甚少。转录组学和高通量测序可以帮助发现癌症诊断靶标并了解生物回路。使用各种基于Web的应用程序的前列腺腺癌(PRAD)数据集(GEPIA,UALCAN,cBioPortal,SRPlot,hTFtarget,基因组浏览器,和MetaCore),我们发现,在原发性前列腺肿瘤中,含dysbindin结构域1(DBNDD1)表达上调与涉及细胞周期的通路密切相关,KEGG的有丝分裂,WIKI,和REACTOME数据库,和前列腺样本中DBND1基因的转录因子结合位点。DBND1基因表达受样本类型的影响,癌症阶段,和不同癌症的启动子甲基化水平,比如PRAD,肝细胞癌(LIHC),和肺腺癌(LUAD)。糖原合成酶激酶(GSK)-3β在双相障碍中的调控及ATP/ITP/GTP/XTP/TTP/CTP/UTP代谢通路与PCa中DBNDD1基因及其共表达基因密切相关。DBND1基因表达与B细胞免疫浸润呈正相关,髓源性抑制细胞(MDSC),M2巨噬细胞,中性粒细胞,而与CD8+T细胞负相关,滤泡辅助性T细胞,M1巨噬细胞,和NK细胞在PCa中。这些发现表明,DBND1不仅可以作为早期PCa的可行预后标志物,而且可以作为免疫疗法的可行预后标志物。
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