摘要
目的 研究胶质母细胞瘤(Glioblastoma, GBM)中盘状蛋白结构域受体1(Discoidin domain receptor 1,DDR1)、Yes相关蛋白1(Yes-associated protein 1,YAP1)、SRY基因相关的HMG盒2(SRY-related high-mobile group box2,SOX2)的表达及临床病理意义。方法 在基因表达交互分析(Gene expression profiling interactive analysis, GEPIA)数据库中对DDR1进行泛癌分析,探究DDR1在GBM中的表达情况。使用中国脑胶质瘤基因组图谱(Chinese glioma genome atlas, CGGA)数据库分析DDR1与YAP1、SOX2、分化簇133(Cluster of differentiation 133,CD133)、神经上皮干细胞蛋白(Neuroepithelial stem cell protein, Nestin)、分化簇44(Cluster of differentiation 44,CD44)的相关性。通过R语言进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析,使用受试者工作曲线(Receiver operating characteristic,ROC)分析DDR1在GBM中的诊断价值。运用免疫组织化学方法检测DDR1、YAP1、SOX2在GBM中的表达情况及它们之间的相关性,通过Kaplan-Meier单因素分析及Cox多因素分析探究GBM预后的影响因素。结果 DDR1在胶质母细胞瘤、食管癌、头颈部鳞状细胞癌等多种肿瘤中高表达,在GBM组织中的表达高于瘤旁组织(P<0.05)。DDR1的表达与YAP1、SOX2、CD133、Nestin、CD44的表达均呈正相关(P均<0.05)。ROC曲线下面积(Area under the curve,AUC)为0.847。DDR1相关的上调差异基因富集在Hippo、Notch、Hedgehog信号通路上。免疫组化结果显示,DDR1、YAP1、SOX2在GBM组织中的表达高于瘤旁组织,其中DDR1表达与年龄、肿瘤大小、手术方式以及Ki-67表达率有关(P均<0.05);YAP1表达与年龄、肿瘤大小、Ki-67表达率有关(P均<0.05);SOX2表达与肿瘤大小、Ki-67表达率有关(P均<0.05)。DDR1与SOX2和YAP1在GBM中的表达均呈正相关(P均<0.05)。DDR1(P=0.055)和SOX2(P<0.05)高表达的患者具有更差的总生存期(Overall survival, OS)。年龄、术后放化疗、Ki-67表达率均为GBM患者中位OS的独立影响因素(P均<0.05)。结论 DDR1可作为GBM的诊断标记物,提示不良预后。
Objective To investigate the expression and significance of discoidin domain receptor 1(DDR1),Yes-associated protein 1(YAP1),and SRY-related high-mobility group box 2(SOX2)in glioblastoma(GBM).Methods Pan-cancer analysis of DDR1 was performed using the Gene Expression Profiling Interactive Analysis(GEPIA)databaseto investigate the expression of DDR1 in GBM.The Chinese Glioma Genome Atlas(CGGA)database was usedto analyze the correlations between DDR1 and YAP1,SOX2,Cluster of Differentiation 133(CD133),Neuroepithelial Stem Cell Protein(Nestin),and Cluster of Differentiation 44(CD44).Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was conductedusing R language,and Receiver Operating Characteristic(ROC)curve analysis was used to evaluate the diagnostic value of DDR1 in GBM.Immunohistochemistrywas employed to detect the expression of DDR1,YAP1,and SOX2 in GBM and their correlation.Kaplan-Meier univariate analysis and Cox multivariate analysis were performed to explore the factors influencing the prognosis of GBM.Results DDR1 was highly expressed in glioblastoma,esophageal cancer,head and neck squamous cell carcinoma,and was higher in GBM tissues than in paratumoral tissues(P<0.05).The expression of DDR1 was positively correlated with the expression of YAP1,SOX2,CD133,Nestin,and CD44(all P<0.05).The ROC curve showed an AUC of 0.847.The differentialgenes related to DDR1 upregulation were enriched inHippo,Notch,and Hedgehog signaling pathways.Immunohistochemistryshowed that the expressions of DDR1,YAP1,and SOX2 in GBM tissues were higher than those in paratumoral tissues,and the expression of DDR1 was related to age,tumor size,surgical approach,and Ki-67 expression rate(all P<0.05).The expression of YAP1 was related to age,tumor size,and Ki-67 expression rate(all P<0.05).SOX2 was related to tumor size and Ki-67 expression rate(P<0.05).The expression of DDR1 was positively correlated with SOX2 and YAP1 in GBM(P<0.05).Patients with high expression of DDR1(P=0.055)and SOX2(P<0.05)had poorer overall survival(OS).Age,postoperative chemoradiotherapy,and Ki-67 expression rate were independent influencing factors of median OS in GBM patients(all P<0.05).Conclusion DDR1 can serve as a diagnostic biomarker for GBM,indicating a poor prognosis.
作者
王玉兰
苏丽萍
吕春莉
张巍
WANG Yulan;SU Liping;LV Chunli;ZHANG Wei(Department of Pathology,the First Affiliated Hospital of Xinjiang Medical University;The State Key Laboratory of Pathogenesis and Prevention of High-Prevalence Diseases in Central Asia,Jointly Established by the Ministry and Provincial Governments,Urumqi 830054,China)
出处
《新疆医科大学学报》
2026年第1期28-35,共8页
Journal of Xinjiang Medical University
基金
新疆维吾尔自治区自然科学基金重点项目(2022D01D72)
省部共建中亚高发病成因与防治国家重点实验室开放课题资助项目(SKL-HIDCA-2022-JZ7)。
