[1]朱家凤,苏　琦.基于 GEO数据筛选卵巢癌细胞对紫杉醇耐药基因及相关分子机制与治疗药物实验探讨[J].现代检验医学杂志,2022,37(01):92-96.[doi:10.3969/j.issn.1671-7414.2022.01.019]
　ZHU Jia-feng,SU Qi.Screening of Paclitaxel Resistant Genes and Related Molecular Mechanisms of Ovarian Cancer Cells Based on GEO Data andExperimental Study of Therapeutic Drugs[J].Journal of Modern Laboratory Medicine,2022,37(01):92-96.[doi:10.3969/j.issn.1671-7414.2022.01.019]
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基于 GEO数据筛选卵巢癌细胞对紫杉醇耐药基因及相关分子机制与治疗药物实验探讨()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年01期
页码:
92-96
栏目:
论　著
出版日期:
2022-01-15

文章信息/Info

Title:
Screening of Paclitaxel Resistant Genes and Related Molecular Mechanisms of Ovarian Cancer Cells Based on GEO Data andExperimental Study of Therapeutic Drugs
文章编号:
1671-7414（2022）01-092-06
作者:
朱家凤; 苏　琦
( 西北妇女儿童医院药剂科，西安 710061)
Author(s):
ZHU Jia-feng; SU Qi
（Department of Pharmacy, Northwest Women’s and Children’s Hospital,Xi’an 710061，China）
关键词:
基因芯片; 紫杉醇耐药; 基因分子机制; 卵巢癌; 血根碱
分类号:
R737.31；R730.43
DOI:
10.3969/j.issn.1671-7414.2022.01.019
文献标志码:
A
摘要:
目的　基于 GEO数据筛选卵巢癌患者对紫杉醇耐药的基因分子机制和治疗药物并进行实验验证。方法　利用 GEO数据库下载卵巢癌紫杉醇耐药基因芯片 GSE28784和 GSE15372，通过 R和 Bioconductor筛选共同差异表达基因并进行 GO和 KEGG分析。分析卵巢癌紫杉醇耐药的基因分子机制，采用 ConnectivityMap筛选紫杉醇耐药卵巢癌患者的治疗药物并进行验证。结果　GSE15372和 GSE28784数据集筛选共同差异表达基因，其中上调 143个，下调 83个。 GO分析显示，共同差异表达基因参与 DNA复制和代谢过程、胆固醇代谢、染色体细胞组分、辅酶结合及腺嘌呤核苷酸结合等分子功能。 KEGG结果显示，共同差异表达基因参与细胞周期、蛋白酶体及萜类化合物骨架生物合成等肿瘤信号通路。与紫杉醇耐药卵巢癌相关的关键基因有 CDK2，MCM4，hMSH2，JUN及 AREG。根据 ConnectivityMap模块分析结果，确定潜在候选药物为血根碱。 1.0，3.0及 5.0 μmol/L血根碱组、紫杉醇组及空白对照组的卵巢癌细胞增殖率和侵袭数目比较，差异具有统计学意义 (F=189.265，95.127，均 P<0.001)。不同浓度血根碱组的卵巢癌细胞增殖率和侵袭数目显著低于紫杉醇组和空白对照组，差异均有统计学意义 (t=2.341~8.720，均 P<0.05)。紫杉醇组与空白对照组的卵巢癌细胞增殖率和侵袭数目比较差异均无统计学意义 (t=0.543，0.389，均 P>0.05)。不同浓度血根碱组组间卵巢癌细胞增殖率和侵袭数目比较，差异具有统计学意义 (t=2.380~5.677，均 P<0.05)。结论　卵巢癌紫杉醇耐药与 CDK2， MCM4，hMSH2，JUN及 AREG关键基因有关，血根碱能有效抑制卵巢癌细胞的增殖、侵袭，有望成为紫杉醇耐药卵巢癌患者的治疗新药。
Abstract:
Objective　The gene molecular mechanism and therapeutic drugs of paclitaxel resistance in ovarian cancer patientswere screened and verified based on GEO data. Methods　The paclitaxel resistant gene chips GSE28784 and GSE15372 ofovarian cancer were downloaded from GEO database. The common differentially expressed genes were screened by R andBioconductor, and analyzed by GO and KEGG. The gene and molecular mechanism of paclitaxel resistance in ovarian cancerwere analyzed and the therapeutic drugs for paclitaxel resistant ovarian cancer patients were screened and verified byConnectivity Map. Results　GSE15372 and GSE28784 data sets screened common differentially expressed genes, of which 143were up-regulated and 83 were down regulated. GO analysis showed that CO differentially expressed genes were involved inDNA replication and metabolic processes, cholesterol metabolism, chromosome cell components, coenzyme binding and adeninenucleotide binding. KEGG results showed that CO differentially expressed genes were involved in tumor signal pathways such ascell cycle, proteasome and terpene skeleton biosynthesis. The key genes associated with paclitaxel resistant ovarian cancer wereCDK2, MCM4, hMSH2, JUN and AREG. According to the analysis results of connectivity Map module, it was determined thatthe potential candidate drug was sanguinarine. The proliferation rate and invasion number of ovarian cancer cells in 1.0, 3.0 and5.0 μmol/L sanguinarine group, the paclitaxel group and the blank control group were significantly different (F=189.265,95.127, P<0.001).The proliferation rate and invasion number of ovarian cancer cells in different concentrations of sanguinarinegroup were significantly lower than those in paclitaxel group and blank control group, the differences were statistacally significant(t=2.341~8.720, all P<0.05). There were no significant difference in the proliferation rate and invasion number of ovariancancer cells between paclitaxel group and blank control group (t=0.543, 0.389, all P>0.05). There were significant difference inthe proliferation rate and invasion number of ovarian cancer cells between different concentrations of sanguinarine groups(t=2.380~5.677, all P<0.05). Conclusion　Paclitaxel resistance in ovarian cancer was related to key genes of CDK2, MCM4,hMSH2, JUN and AREG. Sanguinarine could effectively inhibit the proliferation and invasion of ovarian cancer cells, and isexpected to become a new drug for the treatment of paclitaxel resistant ovarian cancer patients.

参考文献/References:

[1] DOHERTY J A, PERES L C, WANG Chen, etal. Challenges and opportunities in studying theepidemiology of ovarian cancer subtypes [J]. CurrentEpidemiology Reports, 2017, 4(3): 211-220.
[2] 杨俊波, 黄晓洁, 黄春蓉, 等.2003~2013 年某三甲综合医院肿瘤住院患者病死率及死因分析[J]．现代肿瘤医学,2016,24(10):1642-1645.YANG Junbo,HUANG Xiaojie,HUANG Chunrong,etal. The analysis of case fatality rate and death causesof cancer inpatients in a top three general hospitalsfrom 2003 to 2013 [J]. Journal of Modern Oncology,2016,24(10):1642-1645.
[3] WOOPEN H, RICHTER R, CHEKEROV R, et al.Prognostic role of chemotherapy-induced nausea andvomiting in recurrent ovarian cancer patients: results ofan individual participant data meta-analysis in 1213[J].Supportive Care in Cancer, 2020, 28(1): 73-78.
[4] 崔晓娟, 陆晓兰, 冯炜炜．载紫杉醇的聚乙二醇聚丙交酯- 乙交酯聚赖氨酸纳米粒制备及其对耐药卵巢癌细胞的作用[J]. 中国新药与临床杂志, 2020,39(9):552-557.CUI Xiaojuan, LU Xiaolan, FENG Weiwei. Preparationof paclitaxel-loaded mPEG-PLGA-PLL nanoparticlesand their effects on drug-resistant ovarian cancercells [J]. Chinese Journal of New Drugs and ClinicalRemedies,2020,39(9):552-557.
[5] 殷珂欣, 傅志勤, 陈雅卿．卵巢癌紫杉醇耐药机制研究进展[J]. 中华肿瘤防治杂志,2018,25(23):1673-1678.YIN Kexin,FU Zhiqin,CHEN Yaqing. Mechanismof paclitaxel resistance in ovarian cancer[J].Chinese Journal of Cancer Prevention and Treatment,2018,25(23):1673-1678.
[6] 田楠楠, 周磊, 杨丹妮, 等. 沉默RRM1 可逆转乳腺癌细胞MCF-7/R 对紫杉醇的耐药性[J]. 南方医科大学学报,2019,39(3):304-312.TIAN Nannan,ZHOU Lei,YANG Danni,et al.Silencing RRM1 gene reverses paclitaxel resistance inhuman breast cancer cell line MCF-7/R by inducingcell apoptosis [J]. Journal of Southern MedicalUniversity,2019,39(3):304-312.
[7] 李红霞, 关新元．卵巢癌紫杉醇耐药细胞株OC3/TAX300 建立及基因表达谱分析[J]．肿瘤, 2006, 26(8):743-747．LI Hongxia,GUAN Xinyuan. Establishment oftaxol-resistant ovarian carcinoma cell line OC-3/TAX300 and gene expres s ion analys i s [ J ] .Tumor,2006,26(8):743-747.
[8] 李冉红, 岳驰, 魏宝宝, 等.siRNA 沉默X 连锁凋亡抑制蛋白基因逆转人耐紫杉醇卵巢癌细胞耐药性的体内研究[J]. 四川大学学报（医学版）,2020,51(3):320-324.LI Ranhong, YUE Chi, WEI Baobao, et al. In vivostudy of siRNA silencing XIAP gene to reverse taxol-resistance in human ovarian cancer cells[J]. Journalof Sichuan University(Medical Science Edition), 2020,51(3):320-324.
[9] 侯娟, 蒋树立, 滕长财．基于TCGA 数据库卵巢癌患者的miR-301b 表达量与生存状况生物信息学分析[J]. 现代检验医学杂志,2020,35(4):37-40.HOU Juan,JIANG Shuli,TENG Changcai.Bioinformatics analysis of miR-301b expression andsurvival status of patients with ovarian cancer basedon TCGA database[J]. Journal of Modern LaboratoryMedicine,2020,35(4):37-40.
[10] 吴波, 吴媛媛. 基于GEO 数据库筛选卵巢癌细胞A2780 的耐顺铂关键基因及其信号通路[J]. 重庆医学,2020,49(13):2187-2192.WU Bo,WU Yuanyuan. Screening of key genes andsignaling pathways related to cisplatin-resistance inovarian cancer cells A2780 based on GEO database [J].Chongqing Medicine,2020,49(13):2187-2192.
[11] SANTIAGO-O’FARRILL J M, WEROHA S J, HOUXiaonan, et al. Poly(adenosine diphosphate ribose)polymerase inhibitors induce autophagy-mediateddrug resistance in ovarian cancer cells, xenografts, andpatient-derived xenograft models [J]. Cancer, 2020,126(4): 894-907.
[12] 付晓英, 李光, 靳延利．骨髓中CDKN1C 的表达在骨髓增生异常综合征和继发性急性髓系白血病患者中检测的临床意义[J]. 现代检验医学杂志,2017,32(5):36-40.FU Xiaoying,LI Guang,JIN Yanli. Clinical significanceof expression of CDKN1C in bone marrow in patientswith myelodysplastic syndrome and secondary acutemyeloid leukemia[J].Journal of Modern LaboratoryMedicine,2017,32(5):36-40.
[13] GONG Shipeng, CHEN Yongning, MENG Fanliang,et al. RCC2, a regulator of the RalA signaling pathway,is identified as a novel therapeutic target in cisplatinresistantovarian cancer[J]. FASEB Journal, 2019,33(4): 5350-5365.
[14] 靳庆娥, 苏建荣．北京地区汉族女性人群SYK 基因启动子区-803A>T(rs290987)单核苷酸多态性与乳腺癌易感性分析[J]．现代检验医学杂志,2018,33(2):5-7.JIN Qing’e,SU Jianrong. Associations of SYKpromoter-803A >T(rs290987) single nucleotidepolymorphisms with susceptibility to breast cancer ofhan female population in Beijing area[J]. Journal ofModern Laboratory Medicine,2018,33(2):5-7.
[15] HUA Tian, LI Yan, LI Xiaofei, et al. Hypermethylationof mismatch repair gene hMSH2 associates withplatinum-resistant disease in epithelial ovarian cancer[J]. Clinical Epigenetics, 2019, 11(1): 153.
[16] 辛毅娟, 史皆然, 杨柳, 等.ICUs 分离的三种重要病原菌的耐药特性与基因型分析[J]. 现代检验医学杂志,2015,30(5):24-27.XIN Yijuan,SHI Jieran,YANG Liu,et al. Drug resistanceand homological analysis of important clinicalbacterial pathogens [J]. Journal of Modern LaboratoryMedicine,2015,30(5):24-27.
[17] 张素仙, 王妍妍, 张琴, 等．血根碱对紫杉醇耐药卵巢癌A2780/Taxol 细胞生长及TGF-β1/Smad 通路抑制的影响[J]. 中国中西医结合杂志,2018,38(6):717-720.ZHANG Suxian,WANG Yanyan,ZHANG Qin,etal. Sanguinarine inhibited A2780/Taxol cell growthand TGF-beta1/Smad pathway in paclitaxel resistantovarian cancer [J]. Chinese Journal of IntegratedTraditional and Western Medicine,2018,38(6):717-720.
[18] 王恩平, 杨茜, 尹默, 等. 卵巢癌耐药相关信号通路及因子的研究进展[J]. 现代妇产科进展,2017,26(12):943-946.WANG Enping,YANG Qian,YIN Mo,et al.Researchprogress of drug resistance related signaling pathwaysand factors in ovarian cancer[J] Progress in Obstetricsand Gynecology,2017,26(12):943-946.

备注/Memo

备注/Memo:
作者简介：朱家凤（1989-），女，本科，主管药师，研究方向：临床药学，E-mail:562600345@qq.com。
通讯作者：苏琦（1986-），男，本科，主管药师，研究方向：临床药学，E-mail:450216864@qq.com。
更新日期/Last Update: 1900-01-01