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口腔鳞状细胞癌潜在分子机制及预后标志物的鉴定: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.

作者信息

Chujan Suthipong, Kitkumthorn Nakarin, Satayavivad Jutamaad

机构信息

Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand.

Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.

出版信息

J Int Soc Prev Community Dent. 2023 Jun 29;13(3):237-246. doi: 10.4103/jispcd.JISPCD_15_23. eCollection 2023 May-Jun.

Abstract

AIMS AND OBJECTIVES

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的与目标

本研究的目的是揭示口腔癌患者关键的生化途径、预后指标和治疗靶点,以优化治疗策略。

材料与方法

使用生物信息学方法分析五个基因表达综合数据集,以鉴定差异表达基因(DEG)。为确定生物学改变,利用鉴定出的DEG进行基因本体(GO)和KEGG通路分析。通过蛋白质-蛋白质相互作用(PPI)网络分析确定枢纽基因,并使用NetworkAnalyst构建相互作用组。此外,利用人类蛋白质图谱(HPA)和GEPIA2.0数据库评估五个枢纽基因作为预后标志物的用途。另外,使用肿瘤免疫估计资源(TIMER)数据库分析枢纽基因表达与口腔鳞状细胞癌(OSCC)肿瘤免疫细胞浸润之间的相关性。

结果

共鉴定出2071个上调基因和1893个下调基因。GO和通路分析显示,DEG在多个免疫反应术语和炎性细胞因子相互作用中富集。从PPI网络中,鉴定出五个在OSCC中起关键作用的枢纽基因。这些基因包括干扰素调节因子4(IRF4)、趋化因子受体7(CCR7)、肿瘤坏死因子受体超家族成员17(TNFRSF17)、CD27和鞘氨醇-1-磷酸受体4(S1PR4),使用HPA预测它们是OSCC的良好预后标志物。总生存分析显示,五个枢纽基因的低表达与较差的总生存显著相关。我们对肿瘤相关免疫浸润的分析表明,IRF4表达增加与提示所有免疫细胞类型浸润的基因表达谱呈正相关,而CCR7表达增加与中性粒细胞浸润呈负相关。发现CD27、S1PR4和TNFRSF17表达增加与树突状细胞、M0巨噬细胞和中性粒细胞浸润呈负相关。

结论

总之,炎症和免疫反应在OSCC中起重要作用。所有五个枢纽基因都是OSCC预后的良好预测指标,表明它们可作为潜在的治疗靶点和肿瘤标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fe/10411293/bdc9efc83a47/JISPCD-13-237-g001.jpg

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