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A Four-Gene Signature Associated with Radioresistance in Head and Neck Squamous Cell Carcinoma Identified by Text Mining and Data Analysis
Computational and Mathematical Methods in Medicine Pub Date : 2022-9-27 , DOI: 10.1155/2022/5693806
Yongqian Zhang 1 , Hongmin Wang 2 , Feifei Wang 1 , Wenhua Ma 1 , Na Li 1 , Changwen Bo 1 , YingChun Zhao 1 , Li He 1 , Ming Liu 3
Affiliation  

Purpose. Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer globally, and radiotherapy plays a crucial part in its treatment. This study was designed to identify potential genes related to radiation resistance in HNSCC. Method. We first used text mining to obtain common genes related to radiotherapy resistance and HNSCC in published articles. Functional enrichment analyses were conducted to identify the significantly enriched pathways and genes. Protein and protein interactions were performed, and the most significant gene modules were determined; then, genes in the gene modules were validated at transcriptional levels and overall survival. Gene set variation analysis (GSVA) score was calculated, and the association between GSVA score and survival/pathway was estimated. Immune cell infiltration, methylation, and genetic alteration analysis of these genes was conducted in HNSCC patients. Finally, potential sensitive anticancer drugs related to target genes were obtained. Result. We identified 583 common genes through text mining. After further validation, a four-gene signature (EPHB2, SPP1, SERPINE1, and VEGFC) was constructed. The patients with higher GSVA scores have a worse prognosis than those with lower GSVA scores. Differences in methylation of these four genes in HNSCC tumor tissue and normal tissue were compared, with higher methylation levels of EBPH2 and SPP1 in normal tissue and higher methylation levels of SERPINE1 in the tumor. Immune cell infiltration revealed that the increased expression of these genes was closely related to the infiltration level of CD4+ T cell, neutrophil, macrophage, and dendritic cell. Thirty drugs, including 22 positively and eight negatively correlated drugs that most correlated with related genes, were available for treating HNSCC. Conclusion. In this study, we identified four potential genes as well as corresponding drugs that might be related to radioresistance in HNSCC patients. These candidate genes may provide a promising avenue to further elevate radiotherapy efficacy.

中文翻译:

通过文本挖掘和数据分析确定的与头颈部鳞状细胞癌放射抗性相关的四基因特征

目的。头颈部鳞状细胞癌(HNSCC)是全球第六大癌症,放射治疗在其治疗中起着至关重要的作用。本研究旨在鉴定 HNSCC 中与抗辐射性相关的潜在基因。方法. 我们首先使用文本挖掘来获取已发表文章中与放疗抵抗和 HNSCC 相关的常见基因。进行功能富集分析以确定显着富集的途径和基因。进行蛋白质和蛋白质相互作用,确定最重要的基因模块;然后,基因模块中的基因在转录水平和总体存活率上得到验证。计算基因组变异分析 (GSVA) 评分,并估计 GSVA 评分与生存/途径之间的关联。在 HNSCC 患者中进行了这些基因的免疫细胞浸润、甲基化和遗传改变分析。最后,获得了与靶基因相关的潜在敏感抗癌药物。结果. 我们通过文本挖掘确定了 583 个常见基因。经过进一步验证,构建了一个四基因特征(EPHB2、SPP1、SERPINE1 和 VEGFC)。GSVA 评分较高的患者预后较 GSVA 评分较低的患者差。比较这四种基因在HNSCC肿瘤组织和正常组织中甲基化水平的差异,正常组织中EBPH2和SPP1甲基化水平较高,肿瘤中SERPINE1甲基化水平较高。免疫细胞浸润显示这些基因的表达增加与CD4+ T细胞、中性粒细胞、巨噬细胞和树突状细胞的浸润水平密切相关。30 种药物,包括 22 种正相关药物和 8 种与相关基因最相关的负相关药物,可用于治疗 HNSCC。结论. 在这项研究中,我们确定了可能与 HNSCC 患者的放射抗性有关的四种潜在基因以及相应的药物。这些候选基因可能为进一步提高放射治疗效果提供有希望的途径。
更新日期:2022-09-27
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