摘要
目的索拉菲尼是肾癌一线治疗药物,而临床观察发现患者对索拉菲尼药物治疗的应答效果不同。本研究旨在探讨影响肾癌索拉菲尼治疗效果的危险因素,并进一步对PTPN11表达进行对比研究。方法选取北部战区总医院2006-01-01-2016-12-30经口服索拉菲尼治疗〔400mg(200mg×2),口服,2次/d〕的肾癌患者共126例,随访患者临床数据,检测影响索拉菲尼治疗效果的危险因素。进一步选取基线数据差异无统计学意义的长/短无进展生存期(progression-free survival,PFS)的患者各6例,分为非耐药组及耐药组,采用免疫组化分析PTPN11蛋白在肾癌及癌旁的组织分布差异,采用RT-PCR方法检测2组患者PTPN11基因的表达差异。结果单因素分析提示,地区、体质量指数(body mass index,BMI)、美国东部肿瘤协作组(eastern cooperative oncology group,ECOG)一般状况评分、肿瘤转移情况、是否手术治疗、纪念凯特琳癌症中心(memorial sloan-kettering cancer center,MSKCC)评分与患者PFS相关,P<0.05。进一步多因素分析提示,地区(HR=1.627,95%CI为1.039~2.548)、是否手术治疗(HR=0.520,95%CI为0.353~0.767)、MSKCC评分(HR=3.397,95%CI为2.599~4.441)与患者PFS相关,P<0.05;可作为影响索拉菲尼治疗肾癌疗效的独立危险因素。免疫组化提示,肾癌组织中PTPN11高表达,而癌旁组织中表达较低。Real-time PCR结果提示,PTPN11分子耐药组(7.13±0.42)较非耐药组(6.22±0.38)高表达,差异有统计学意义,t=3.827,P=0.03。结论肾癌患者所处地区、是否手术治疗及MSKCC评分等可能是影响患者使用索拉菲尼治疗效果的独立危险因素,且PTPN11基因表达可能与肾癌索拉菲尼耐药相关。
OBJECTIVE Sorafenib is the first-line treatment for kidney cancer,and clinical observations showed that patients have different effects on the treatment of sorafenib.This study aimed to discuss the risk factors affecting the therapeutic effect of sorafenib in kidney cancer and reporte a comparative study performed on the expression of PTPN11.METHODS A total of 126 patients with renal cell carcinoma treated with oral sorafenib(400 mg,orally,1/12 h)from January 1,2006 to December 30,2016 were enrolled.Follow-up patient’s clinical data to discuss risk factors affecting the efficacy of sorafenib treatment,P<0.05 was considered statistically significant.Six patients with long/short PFS with no significant difference in baseline data were divided into non-resistance group and drug-resistant group.Immunohistochemical method was used to analyze of the difference in the distribution of PTPN11 protein in renal cancer and adjacent tissues.Real-time PCR was used to detect the difference of PTPN11 gene expression between the two groups.RESULTS Univariate analysis showed that regional,BMI,ECOG score,tumor metastasis,surgical treatment and MSKCC score were associated with PFS which was statistically significant(P<0.05).Further multivariate analysis suggested that the area(HR=1.627,95%CI:1.039-2.548),whether surgical treatment(HR=0.520,95%CI:0.353-0.767),MSKCC score(HR=3.397,95%CI:2.599-4.441)was associated with PFS which is statistically significant(P<0.05).The results of immunohistochemistry indicated that PTPN11 protein was highly expressed in adjacent tissues of renal cell carcinoma.Real-time PCR results indicated that the PTPN11 molecular expression in resistance group(7.13±0.42)was higher than that of the non-resistant group(6.22±0.38),and the difference was significant(t=3.827,P=0.03).CONCLUSION The location of patients with renal cell carcinoma as well as both surgical treatment and MSKCC score can be used as independent risk factors for the treatment of renal cancer with sorafenib,and PTPN11 gene expression may be a
作者
韩涛
刘兆喆
谢晓冬
HAN Tao;LIU Zhao-zhe;XIE Xiao-dong(Department of Oncology,General Hospital of Northern Theater Command,Shenyang110016,P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第11期910-914,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81702622)。
