CAJ | 학술논문

目的：了解卵巢癌患者在铂类治疗过程中产生获得性耐药相关基因表达动态变化的情况，为临床预后的预测及个体化治疗奠定理论基础。方法采用Benjamini-Hochberg（BH）法对源于TCGA数据库（The Cancer Genome Atlas）的256例敏感和耐药患者的卵巢癌全基因表达谱数据进行差异表达基因筛选。采用DAVID软件中的KEGG模块对筛选出的差异基因进行通路富集，筛选出P<0.05的通路，对筛选出的通路所包含的基因采用成组t检验找出差异显著的基因（P<0.05）。对筛选出的基因采用COREMINE工具进行文本挖掘，找出与多药耐药及肿瘤耐药存在线性相关的基因，将其与患者预后进行分析，确定存在差异显著的基因。采用实时荧光定量PCR法检测所筛选出的基因在裸鼠诱导耐药模型不同给药阶段的表达变化情况。结果 BH法共筛选出306个差异表达基因，其中上调基因110个，下调基因196个。DAVID软件的KEGG模块分别筛选出5条上调及4条下调通路，成组t检验筛选出有差异的基因共37个，其中上调基因18个，下调基因19个。COREMINE工具检索出与多药耐药及肿瘤耐药存在线性相关的上调基因为ITPA、IMPDH2、RPS7、PDE5A和PDE4D，下调基因为GNAS、CFTR、BUB3、PRKDC、RBL2、SMC1A、CALR、CCNE2及CHEK1。生存分析结果提示CALR及PRKDC基因的表达与患者生存时间有关，CALR和PRKDC基因高表达组的患者生存时间长于低表达组。qRT-PCR检测发现，CALR和PRKDC基因随顺铂注射次数增多，在SKOV3-GFP及SKOV3/DDP英肿瘤组织中的表达量逐渐降低。结论 CALR与PRKDC基因可能与卵巢癌铂类耐药及患者的预后密切相关，且随着耐药的产生，CALR和PRKDC基因的表达量逐渐降低。
목적：료해란소암환자재박류치료과정중산생획득성내약상관기인표체동태변화적정황，위림상예후적예측급개체화치료전정이론기출。방법채용Benjamini-Hochberg（BH）법대원우TCGA수거고（The Cancer Genome Atlas）적256례민감화내약환자적란소암전기인표체보수거진행차이표체기인사선。채용DAVID연건중적KEGG모괴대사선출적차이기인진행통로부집，사선출P<0.05적통로，대사선출적통로소포함적기인채용성조t검험조출차이현저적기인（P<0.05）。대사선출적기인채용COREMINE공구진행문본알굴，조출여다약내약급종류내약존재선성상관적기인，장기여환자예후진행분석，학정존재차이현저적기인。채용실시형광정량PCR법검측소사선출적기인재라서유도내약모형불동급약계단적표체변화정황。결과 BH법공사선출306개차이표체기인，기중상조기인110개，하조기인196개。DAVID연건적KEGG모괴분별사선출5조상조급4조하조통로，성조t검험사선출유차이적기인공37개，기중상조기인18개，하조기인19개。COREMINE공구검색출여다약내약급종류내약존재선성상관적상조기인위ITPA、IMPDH2、RPS7、PDE5A화PDE4D，하조기인위GNAS、CFTR、BUB3、PRKDC、RBL2、SMC1A、CALR、CCNE2급CHEK1。생존분석결과제시CALR급PRKDC기인적표체여환자생존시간유관，CALR화PRKDC기인고표체조적환자생존시간장우저표체조。qRT-PCR검측발현，CALR화PRKDC기인수순박주사차수증다，재SKOV3-GFP급SKOV3/DDP영종류조직중적표체량축점강저。결론 CALR여PRKDC기인가능여란소암박류내약급환자적예후밀절상관，차수착내약적산생，CALR화PRKDC기인적표체량축점강저。
Objective To study the dynamic expression of resistance genes during chemotherapy resistance process,so as to provide evidences for exploring reversal targets and reversal treatment. Methods Adopt Benjamini-Hochberg(BH)to analyse expression profile data of ovarian cancer who provided by TCGA,then use KEGG of DAVID to enrich the pathway,then employ T test to measure them again,use COREMINE to select some genes which is associated with multiple drug resistant and drug resistance of neoplasm.Take the differentially expressed gene to conduct survival analysis,find out the genes which is significant. Then employ qRT-PCR to examine the expression of them in SKOV3-GFP and SKOV3/DDPiitumor. Result 306 differentially expressed genes were found in Microarray, of which 110 had increased expression and 196 had low expression. KEGG of DAVID enrichment 5 up-regulate-pathway and 4 down-regulate-pathway.T test sift out 18 up-regulate genes and 19 down-regulate genes.COREMINE search out 5 up-regulate genes,for example:ITPA、IMPDH2、RPS7、PDE5A and PDE4D,down-regurate genes as GNAS、CFTR、BUB3、PRKDC、RBL2、SMC1A、CALR、CCNE2 and CHEK1. Survival analysis shows that overall survival was longer when comparing high expression team of CALR and PRKDC with low expression team.Expression of CALR and PRKDC gradually reduces as Cisplatin injection times increase in SKOV3-GFP and SKOV3/DDP ii tumor. Conclusion Expression of CALR and PRKDC may be associated with cisplatin resistance.So reduc-ing expression of CALR and PRKDC mean that these ovarian cancer patientsmay have resistance to cisplatin.