基因突变与转移性肾透明细胞癌患者VEGF靶向治疗预后的关系  

ASSOCIATION OF GENE MUTATION WITH THE PROGNOSIS OF PATIENTS WITH METASTATIC RENAL CLEAR CELL CARCINOMA RECEIVING VASCULAR ENDOTHELIAL GROWTH FACTOR-TARGETED THERAPY

作　　者：刘睿[1] 张铭鑫 李丹[1] 梁晔[1] 梁志娟 王丽萍[1] 牛海涛[1] LIU Rui;ZHANG Mingxin;LI Dan;LIANG Ye;LIANG Zhijuan;WANG Liping;NIU Haitao(Department of Urology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院泌尿外科,山东青岛266003

出　　处：《精准医学杂志》2021年第3期239-242,共4页Journal of Precision Medicine

基　　金：国家自然科学基金资助项目(82071750)。

摘　　要：目的基于全外显子测序技术筛选肾透明细胞癌高频率突变基因,分析其与患者血管内皮生长因子(VEGF)靶向治疗预后的关系。方法选取我院拟接受舒尼替尼或索拉非尼治疗的15例转移性肾透明细胞癌患者的肿瘤石蜡组织切片,进行全外显子测序。纳入TCGA数据库中5例符合入组标准的患者,共计20例。分析各基因突变和患者预后的关系,利用Kaplan-Meier方法进行生存分析,并采用Log-rank进行差异性检验,以P<0.05为差异具有统计学意义。结果分析显示,VHL、PBRM 1、SETD2及PRDM 16基因发生突变分别为11、7、4、3例,突变频率与TCGA数据库中肾透明细胞癌的基因突变频率分布基本相符。与PBRM 1基因野生型患者相比,PBRM 1基因突变型患者无进展生存期(PFS)较长(χ^(2)=5.45,P<0.05;HR=0.34,95%CI=0.12~0.96),PRDM16基因突变型患者PFS也较长(χ^(2)=8.22,P<0.05;HR=0.09,95%CI=0.01~0.76);但是高频率突变的VHL和SETD 2基因对于患者PFS无明显影响。结论在众多突变基因中,PBRM 1和PRDM 16基因突变与转移性肾透明细胞癌患者VEGF靶向药物治疗预后密切相关,提示此类患者临床应用舒尼替尼和索拉非尼等靶向药物获益更多,此从基因层面为临床用药提供了理论依据。Objective To screen out high-frequency mutation genes in renal clear cell carcinoma based on whole-exome sequencing,and to investigate their association with the prognosis of patients receiving vascular endothelial growth factor(VEGF)-targeted therapy.Methods Paraffin sections of tumor tissue were collected from 15 patients with metastatic renal clear cell carcinoma who planned to receive sunitinib or sorafenib in our hospital,and whole-exome sequencing was performed.Five patients in the TCGA database who met the inclusion criteria were enrolled in this study,resulting in a total number of 20 patients.The association between each gene mutation and prognosis was analyzed;the Kaplan-Meier method was used for survival analysis,and the log-rank test was used for difference analysis;P<0.05 was considered statistically significant.Results The analysis showed that VHL,PBRM 1,SETD 2,and PRDM 16 gene mutations were observed in 11,7,4,and 3 patients,respectively,and the mutation frequency was basically consistent with the frequency distribution of gene mutations in renal clear cell carcinoma in the TCGA database.Compared with the patients with wild-type PBRM 1 gene,the patients with PBRM 1 gene mutation had longer progression-free survival(PFS)(χ^(2)=5.45,P<0.05;HR=0.34,95%CI=0.12-0.96),and the patients with PRDM 16 gene mutation also had longer PFS(χ^(2)=8.22,P<0.05;HR=0.09,95%CI=0.01-0.76),while the high-frequency mutations of the VHL and SETD 2 genes had no significant influence on PFS.Conclusion Among the various mutation genes,only PBRM 1 and PRDM 16 gene mutations are closely associated with the prognosis of patients with metastatic renal clear cell carcinoma receiving VEGF-targeted therapy,suggesting that such patients may obtain more benefits from the clinical application of targeted drugs such as sunitinib and sorafenib,which provides a theoretical basis for clinical medication at the gene level.

关 键 词：癌 肾细胞 血管内皮生长因子类 分子靶向治疗 药物疗法 预后 突变 全外显子组测序 

分 类 号：R737.11[医药卫生—肿瘤] R730.26[医药卫生—临床医学]