口腔鳞状细胞癌的潜在分子机制和预后标志物的鉴定: 一项生物信息学分析。
Identification of Potential Molecular Mechanisms and Prognostic Markers for Oral Squamous Cell Carcinoma: A Bioinformatics Analysis.
发表日期:2023
作者:
Suthipong Chujan, Nakarin Kitkumthorn, Jutamaad Satayavivad
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
本研究的目标是揭示口腔癌患者关键的生化途径、预后指标和治疗靶点,以提升治疗策略。使用生物信息学方法分析了五个基因表达组学数据集,以识别差异表达基因(DEGs)。通过使用已识别的DEGs,进行基因本体论(GO)和KEGG途径分析,确定生物学改变。使用蛋白质相互作用(PPI)网络分析确定了中枢基因,并使用NetworkAnalyst构建了交互组。此外,使用人类蛋白质图谱(HPA)和GEPIA2.0数据库评估了五个中枢基因作为预后标志物的潜力。此外,利用tumor immune estimation resource (TIMER)数据库分析了中枢基因表达与口腔鳞状细胞癌(OSCC)肿瘤的免疫细胞浸润之间的相关性。共识别出2071个上调基因和1893个下调基因。GO和途径分析显示,差异表达基因富集在多个免疫反应术语和炎症细胞因子的相互作用中。从PPI网络中识别了五个在OSCC中起关键作用的中枢基因。其中包括干扰素调节因子4 (IRF4)、趋化因子受体7 (CCR7)、TNF受体超家族成员17 (TNFRSF17)、CD27和鞘磷脂-1-磷酸受体4 (S1PR4),通过HPA预测它们有利于OSCC的预后标志物。整体生存分析显示,这五个中枢基因的低表达与更差的整体生存显著相关。我们对肿瘤相关免疫浸润分析显示,增加的IRF4表达与所有免疫细胞类型的浸润基因表达谱呈正相关,而CCR7表达的增加与中性粒细胞浸润呈负相关。发现CD27、S1PR4和TNFRSF17的表达增加与树突状细胞、M0型巨噬细胞和中性粒细胞浸润呈负相关。总之,炎症和免疫反应在OSCC中起重要作用。所有五个中枢基因都是OSCC预后的良好预测因子,表明它们有望作为潜在的治疗靶点和肿瘤标志物使用。
Copyright: © 2023 Journal of International Society of Preventive and Community Dentistry.
The goal of this study was to uncover crucial biochemical pathways, prognostic indicators, and therapeutic targets in patients with oral cancer in order to enhance therapy strategies.Five gene expression omnibus datasets were analyzed by using bioinformatics approaches to identify differentially expressed genes (DEGs). To determine biological alterations, gene ontology (GO) and KEGG pathway analyses were implied using the identified DEGs. Hub genes were determined using protein-protein interaction (PPI) network analysis and an interactome was constructed using NetworkAnalyst. Furthermore, five hub genes were evaluated for use as prognostic markers by using the human protein atlas (HPA) and the GEPIA2.0 database. In addition, the correlations between hub-gene expression and immune cell infiltration of oral squamous cell carcinoma (OSCC) tumors were analyzed using the tWumor immune estimation resource (TIMER) database.A total of 2071 upregulated genes and 1893 downregulated genes were identified. GO and pathway analysis showed DEGs were enriched in multiple immune response terms and interaction of inflammatory cytokines. From the PPI network, five hub genes were identified that have a crucial role in OSCC. These included interferon regulatory factor 4 (IRF4), chemokine receptor 7 (CCR7), TNF receptor superfamily member 17 (TNFRSF17), CD27, and sphingosine-1-phosphate receptor 4 (S1PR4), which were predicted to be favorable prognostic markers for OSCC using HPA. Overall survival analysis revealed that low expression of the five hub genes was significantly associated with worse overall survival. Our analysis of tumor-associated immune infiltration revealed that increased IRF4 expression was positively correlated with the gene expression profiles suggestive of infiltration of all immune cell types, whereas increased CCR7 expression was negatively correlated with neutrophil infiltration. Increased expression of CD27, S1PR4, and TNFRSF17 was found to be negatively correlated with dendritic cell, M0 macrophage, and neutrophil infiltration.In summary, inflammation, and the immune response play an important role in OSCC. All five hub genes were good predictors of OSCC prognosis, suggesting that they could be used as potential therapeutic targets and tumor markers.Copyright: © 2023 Journal of International Society of Preventive and Community Dentistry.