Department of Medical Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Mol Genet Genomic Med. 2020 Apr;8(4):e1160. doi: 10.1002/mgg3.1160. Epub 2020 Feb 12.
Excessive or prolonged usage of dexamethasone can cause serious side effects, but few studies reveal the related mechanism. Dexamethasone work differently in blood tumors and solid tumors, and the cause is still obscure. The aims of this study was to identify potential biomarkers associated with the side effects of dexamethasone in different tumors.
Gene Expression Omnibus database (GEO) datasets of blood tumors and solid tumors were retrieval to selected microarray data. The differentially expressed genes (DEGs) were identified. Gene ontology (GO) and pathway enrichment analyses, and protein-protein interaction (PPI) network analysis were performed.
One hundred and eighty dexamethasone-specific DEGs (92 up and 88 downregulated) were obtained in lymphoma cell samples (named as DEGs-lymph), including APOD, TP53INP1, CLIC3, SERPINA9, and C3orf52. One hundred and four specific DEGs (100 up and 4 downregulated) were identified in prostate cancer cell samples (named as DEGs-prostate), including COL6A2, OSBPL5, OLAH, OGFRL1, and SLC39A14. The significantly enriched GO terms of DEGs-lymph contained cellular amino acid metabolic process and cell cycle. The most significantly enriched pathway of DEGs-lymph was cytosolic tRNA aminoacylation. The DEGs-prostate was enriched in 39 GO terms and two pathways, and the pathways were PPARA activates gene expression Homo sapiens, and insulin resistance. The PPI network of DEGs-lymph gathered into two major clusters, WARS1 and CDC25A were representatives for them, respectively. One cluster was mainly involved in cytosolic tRNA aminoacylation, aminoacyl-tRNA biosynthesis and the function of amino acid metabolism; another was associated with cell cycle and cell apoptosis. As for the PPI network of DEGs-prostate, HELZ2 was the top nodes involved in the most protein-protein pairs, which was related to the pathway of "PPARA activates gene expression Homo sapiens."
WARS1 and CDC25A might be potential biomarkers for side effects of dexamethasone in lymphoma, and HELZ2 in prostate cancer.
地塞米松的过度或长期使用会导致严重的副作用，但很少有研究揭示其相关机制。地塞米松在血液肿瘤和实体肿瘤中的作用不同，其原因尚不清楚。本研究旨在鉴定与地塞米松在不同肿瘤中的副作用相关的潜在生物标志物。
从基因表达综合数据库（GEO）中检索血液肿瘤和实体肿瘤的微阵列数据集，以选择微阵列数据。鉴定差异表达基因（DEGs）。进行基因本体（GO）和通路富集分析以及蛋白质-蛋白质相互作用（PPI）网络分析。
从淋巴瘤细胞样本中获得 180 个地塞米松特异性 DEGs（92 个上调和 88 个下调）（命名为 DEGs-淋巴瘤），包括 APOD、TP53INP1、CLIC3、SERPINA9 和 C3orf52。从前列腺癌细胞样本中鉴定出 104 个特异性 DEGs（100 个上调和 4 个下调）（命名为 DEGs-前列腺），包括 COL6A2、OSBPL5、OLA、OGFRL1 和 SLC39A14。DEGs-淋巴瘤的显著富集 GO 术语包括细胞内氨基酸代谢过程和细胞周期。DEGs-淋巴瘤最显著富集的途径是胞质 tRNA 氨酰化。DEGs-前列腺富集了 39 个 GO 术语和两个途径，这些途径是 PPARA 激活基因表达智人，和胰岛素抵抗。DEGs-淋巴瘤的 PPI 网络聚集为两个主要集群，WARS1 和 CDC25A 分别是它们的代表。一个集群主要参与胞质 tRNA 氨酰化、氨酰-tRNA 生物合成和氨基酸代谢功能；另一个与细胞周期和细胞凋亡有关。对于 DEGs-前列腺的 PPI 网络，HELZ2 是涉及最多蛋白质-蛋白质对的顶级节点，与“PPARA 激活基因表达智人”途径有关。
WARS1 和 CDC25A 可能是淋巴瘤中地塞米松副作用的潜在生物标志物，HELZ2 可能是前列腺癌中地塞米松副作用的潜在生物标志物。
