Tan Yishuai, Zhou Jiao, Liu Kai, Liu Ruowu, Zhou Jing, Wu Zhenru, Li Linke, Zeng Jiaqi, Feng Xuxian, Dong Biao, Du Jintao
Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
West China School of Pharmacy, Sichuan University, Chengdu, China.
Front Oncol. 2024 May 24;14:1354940. doi: 10.3389/fonc.2024.1354940. eCollection 2024.
Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survival models. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistent with the DEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC.
鼻咽癌(NPC)通常在晚期被诊断出来,在东南亚和中国东南部发病率很高。然而,公共数据库中鼻咽癌患者生存数据的可用性有限,导致通过构建Kaplan-Meier曲线来预测鼻咽癌生存的研究不够严谨。这些研究主要依赖于具有无进展生存期(PFS)信息的少量鼻咽癌患者样本,或几乎没有鼻咽癌患者的头颈部鳞状细胞癌(HNSCC)研究数据。因此,我们对从基因表达综合数据库(GEO)下载的11个数据集(46个正常(对照)样本与160个肿瘤(NPC)样本)中的RNA表达谱以及中山大学马骏提供的生存数据进行了联合分析。然后,使用STRING数据库进行差异分析、基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析和网络分析。之后,筛选出2142个上调的差异表达基因(DEG)和3857个下调的DEG。其中25个被确定为枢纽基因,它们富集于几个通路(纤毛运动、细胞外基质结构成分、同源重组和细胞周期)。利用我们从GEO数据库积累的综合数据集,我们对DEG进行了生存分析,并随后构建了生存模型。鉴定出7个DEG(RASGRP2、MOCOS、TTC9、ARHGAP4、DPM3、CD37和CD72),它们与鼻咽癌的生存预后密切相关。最后,进行了qRT-PCR、WB和IHC实验,以证实RASGRP2的表达升高以及TTC9、CD37、DPM3和ARHGAP4的表达降低,这与DEG分析结果一致。总之,我们的研究结果通过大数据生物信息学分析为鼻咽癌的新型预后生物标志物提供了见解,这表明它们可能成为鼻咽癌治疗中的特殊靶点。