生物信息学和孟德尔随机化分析口腔鳞状细胞癌差异表达基因与患者预后的相关性  

Bioinformatic and Mendelian Randomization Analyses of Correlation Between Differentially Expressed Genes and Prognosis of Oral Squamous Cell Carcinoma Patients

作　　者：刘茂林[1,2] 宋晓娜 刘雅琪 史舒瑄 宋国华 LIU Maolin;SONG Xiaona;LIU Yaqi;SHI Shuxuan;SONG Guohua(Asset Management Department,Shanxi Medical University,Taiyuan 030001,China;Shanxi Key Laboratory of Laboratory Animal and Human Disease Animal Model,Center for Laboratory Animals,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学资产管理部,太原030001 [2]山西医科大学实验动物中心,实验动物与人类疾病动物模型山西省重点实验室,太原030001

出　　处：《肿瘤防治研究》2025年第2期133-141,共9页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(31772551,31970513);山西省科技创新人才团队项目(202204051002032);山西省高等教育“工程”科技引导(BYJL016)。

摘　　要：目的通过生物信息学和孟德尔随机化分析口腔鳞状细胞癌(OSCC)中的差异表达基因,探讨其与OSCC预后的相关性。方法TCGA数据库和数据集GSE138206筛选OSCC共同的差异基因,并利用孟德尔随机化分析它们之间的关系,进一步通过Cox风险回归分析差异基因的预后价值,对预后价值高的基因进行单基因差异分析后进一步评估其生物学功能。结果两个数据库共筛选出147个共同差异基因,双样本孟德尔随机化结果显示GREM2与口腔鳞状细胞癌风险增加有关,SH3BGRL2与其风险减小有关,此外DKK1、CCL11和HOXC6是OSCC预后的独立标志基因,而DKK1的预测结果与实际结果的一致性最好。KEGG富集通路显示DKK1可能参与花生四烯酸代谢与亚油酸代谢。此外,DKK1与Tgd和Th2细胞呈正相关,与PDC、Cytotoxic、Mast、CD8 T、TFH、B、T和Th17细胞呈负相关。结论GREM2与OSCC风险增加有关、DKK1在OSCC中高表达且与不良预后相关,其可能参与调控OSCC中花生四烯酸与亚油酸代谢及免疫细胞浸润进程,为后续研究奠定了基础。Objective Differentially expressed genes in oral squamous cell carcinoma(OSCC)were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC.Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC,and their relationship was analyzed by using Mendelian randomization.The prognostic value of differential genes was further analyzed by Cox risk regression.The biological function of genes with high prognostic value was further evaluated by single gene differential analysis.Results A total of 147 common differential genes were screened from the two databases.Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC.In addition,SH3BGRL2 was associated with a decreased risk of OSCC,and DKK1,CCL11,and HOXC6 were considered as independent prognostic markers of OSCC.The predicted results of DKK1 were consistent with the actual results.KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism.Furthermore,DKK1 showed positive correlations with Tgd and Th2 cells,while displaying negative associations with PDC,Cytotoxic cells,Mast cells,CD8 T cells,TFH cells,B cells,T cells,and Th17 cells.Conclusion GREM2 is associated with an increased risk of OSCC.DKK1 is highly expressed in OSCC and associated with poor prognosis,which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.

关 键 词：生物信息 孟德尔随机化 口腔鳞状细胞癌 Cox风险回归分析 

分 类 号：R739.8[医药卫生—肿瘤]