Skp2高表达与骨肉瘤患者新辅助化疗耐药之间的联系  

Correlation of Skp2 high expression with neoadjuvant chemotherapy resistance in patients with osteosarcoma

作　　者：许多辉 丁路[2] 余伟 宋正南 白靖平 XU Duohui;DING Lu;YU Wei;SONG Zhengnan;BAI Jingping(Department of Bone and Soft Tissue Oncology,the Third Clinical Medical College of Xinjiang Medical University,Xinjiang Uygur Autonomous Region,Urumqi830000,China;The first Department of Orthopedics,the Fifth Clinical Medical College of Xinjiang Medical University,Xinjiang Uygur Autonomous Region,Urumqi830000,China)

机构地区：[1]新疆医科大学第三临床医学院骨软科,新疆乌鲁木齐830000 [2]新疆医科大学第五临床医学院骨一科,新疆乌鲁木齐830000

出　　处：《中国医药导报》2020年第31期35-39,共5页China Medical Herald

基　　金：新疆维吾尔自治区创新环境(人才、基地)建设专项(自然科学基金)资助项目(2018D01C301)。

摘　　要：目的探索Skp2在骨肉瘤新辅助化疗耐药中的作用。方法收集GSE126209,GSE16089和TCGA数据中骨肉瘤和耐药骨肉瘤的基因表达谱。鉴定Skp2对骨肉瘤耐药的机制。收集2018年2月-2019年6月新疆医科大学第三临床医学院收治的OS患者17例,按肿瘤细胞坏死率(TCNR)≥90%为非耐药,TCNR<90%为耐药分组,其中,非耐药肿瘤组织11例和耐药肿瘤组织6例;非耐药癌旁组织11例和耐药癌旁组织6例。RT-qPCR和Western-blot检测骨肉瘤癌组织及癌旁组织中的Skp2及相关基因的mRNA和蛋白表达情况。结果Skp2在骨肉瘤组织和甲氨蝶呤耐药细胞中均差异表达上调,Skp2参与细胞周期、FOXO通路等。分子实验结果示耐药骨肉瘤组织中Skp2、AKT的表达显著上升(P<0.05);p27、FOXO1、E-Cadherin在耐药肿瘤组织中的表达显著降低(P<0.05)。Cox分析示Skp2(HR=1.52,95%CI:0.67~3.46,P=0.31)、AKT(HR=1.04,95%CI:0.48~2.28,P=0.93)、p21(HR=1.09,95%CI:0.51~2.34,P=0.83)、p27(HR=1.50,95%CI:0.67~3.38,P=0.32)可能是影响骨肉瘤预后的风险因素。结论Skp2参与骨肉瘤新辅助化疗耐药产生,并与细胞周期和FOXO通路有关。Objective To explore the effect of Skp2 in neoadjuvant chemotherapy resistance of osteosarcoma.Methods Gene expression profiles of osteosarcoma and resistant osteosarcoma were collected from GSE126209,GSE16089 and TCGA datasets.The mechanisms of Skp2 resistance to osteosarcoma were identified.From February 2018 to June 2019,17 patients with osteosarcoma admitted to the Third Clinical Medical College of Xinjiang Medical University were collected,non-drug resistance was defined as tumor cell necrosis rate(TCNR)≥90%,and drug resistance was defined as TCNR<90%,11 cases of including non-drug resistant tumor tissues and 6 cases of drug resistant tumor tissues;11 cases of non-drug-resistant paracancer tissues and 6 cases of drug-resistant paracancer tissues.RT-qPCR and Western-blot were used to detect mRNA and protein expression of Skp2 and related genes in osteosarcoma carcinoma tissues and adjacent tissues.Results The Skp2 was up-regulated in both osteosarcoma tissue and Methotrexate resistant cells.It was involved in cell cycle and FOXO pathway.Molecular experimental results showed that Skp2 and AKT expressions in drug-resistant osteosarcoma tissues were significantly increased(P<0.05);the expressions of p27,FOXO1 and E-Cadherin in resistant osteosarcoma were significantly lower(P<0.05).Cox analysis indicated that Skp2(HR=1.52,95%CI:0.67-3.46,P=0.31),AKT(HR=1.04,95%CI:0.48-2.28,P=0.93),p21(HR=1.09,95%CI:0.51-2.34,P=0.83),p27(HR=1.50,95%CI:0.67-3.38,P=0.32)may be risk factors for prognosis of osteosarcoma.Conclusion Skp2 is involved in neoadjuvant chemotherapy resistance and in osteosarcomd and is associated with the cell cycle and FOXO pathway.

关 键 词：骨肉瘤 S期激酶相关蛋白2 化疗耐药 细胞周期 

分 类 号：R738.1[医药卫生—肿瘤]