血管内皮生长因子及其受体在人皮肤黑素瘤的组学数据分析  

Transcriptome Data Analysis of VEGFA,VEGFB and Their Receptors in Human Skin Melanoma Cells

作　　者：姚战非[1] 张雪梅[1] 马枞 YAO Zhanfei;ZHANG Xuemei;MA Cong(Department of Dermatology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000,China)

机构地区：[1]内蒙古民族大学附属医院皮肤科

出　　处：《中国皮肤性病学杂志》2019年第6期628-633,共6页The Chinese Journal of Dermatovenereology

摘　　要：目的研究血管内皮生长因子(VEGFA、VEGFB)及其受体KDR、FLT1在人皮肤黑素瘤中的基因组学、转录组学变异及其与临床预后的相关性。方法利用TC-GA数据库,分析VEGFA、VEGFB及其受体KDR、FLT1的基因组学、转录组学突变频谱及其变化与临床预后的相关性;通过生物信息学筛选其共同相关基因,探索其可能的分子机制。结果在TCGA数据库同时具备基因组信息和转录组信息的287例黑素瘤样本中.VEGFA基因突变率为5.92%,VEGFB突变率为2.09%,KDR突变率为16.72%,FLT1突变率为12.54%,其突变与黑素瘤患者生存期无明显关系,转录组数据显示VEGFA mRNA表达上调率为3.48%,VEGFB mRNA表达上调率为3.83%,KDR mRNA表达上调率为2.09%,FLT1 mRNA表达上调率为3.83%,VEGFB表达上调与患者临床预后显著相关,表达上调和表达无变化者生存中位数分别为33.9个月和94.91个月(P=6.870e-4),VEGFA和KDR表达上调对患者预后有影响趋势,但差异无统计学意义。生物信息学分析显示CMTM1、QKI、BACH1可能是影响VEGFA/B作用的关键基因,提示其可能作为抗血管生成治疗的靶位点。结论VEGFA、VEGFB及其受体KDR、FLT1在人黑素瘤中存在着拷贝数扩增和表达量的显著上调,VEGFB的变化与患者临床预后显著相关,提示其可能在黑素瘤的血管生成中发挥着重要作用。本研究为临床黑素瘤的治疗提供了有益线索。Objective To study the genomic and transcriptomic rariations of vascular endothelial growth factor ( VEGFA, VEGFB) and their receptors (KDR, FLT1) in human skin melanoma, and the correlation between the variations and clinical outcome of patients with melanoma. Methods TCGA database was used to analyze the genomic and transcriptome variations of VEGFA/VEGFB/KDR/FLT1 and their relation with clinical outcome. The co-related genes were screened for possible molecular mechanisms through bioinformatics. Results In the 287 cases of melanoma samples with genome and transcriptome information, the mutation rate of VEGFA ( 5. 92%), DEGFB(2. 09%), KDR ( 16. 72%), FLT1 ( 12. 54%) had no obvious relation with the survival of melanoma patients. VEGFA, VEGFB, KDR, FLT1 mRNA were up-regulated by 3. 48%, 3. 83%, 2. 09%, 3. 83% in patients respectively. The upregulation of VEGFB expression was related with the outcomes of the patients with melanoma significantly ( P = 6. 870e - 4 ), and the median survival of the patients with and without up-regulated VEGFB were 33. 9 months and 94. 91 months, respectively. VEGFA and KDR expression level had similar effects on the prognosis of patients, without statistical significance. Bioinformatics analysis showed that CMTM1 , QKI, BACH1 might be the key genes that affect VEGFA/B function, suggesting that the genes might act as targets for anti-angiogenesis therapy. Conclusion There are genomic copy number amplification and mRNA expression upregulation of VEGFA , VEGFB and their receptors KDR, FLT1 in human melanoma. There is significant correlation between the upregulation of VEGFB mRNA and the melanoma patients;prognosis, suggesting the gene may play an important role in angiogenesis of melanoma. This study provides a helpful clue for the treatment of malignant melanoma.

关 键 词：黑素瘤 血管内皮生长因子 生物信息学分析 突变 临床预后 

分 类 号：R739.5[医药卫生—肿瘤]