[1]陈 霄,吴小颖,安 明.宫颈癌组织中NEK2 和circPITX1 的表达水平与放疗敏感度及预后的相关性研究[J].现代检验医学杂志,2023,38(01):27-32.[doi:10.3969/j.issn.1671-7414.2023.01.006]
 CHEN Xiao,WU Xiao-ying,AN Ming.Correlation between the Expression Levels of NEK2 and CircPITX1 and Radiotherapy Sensitivity and Prognosis in Cervical Cancer[J].Journal of Modern Laboratory Medicine,2023,38(01):27-32.[doi:10.3969/j.issn.1671-7414.2023.01.006]
点击复制

宫颈癌组织中NEK2 和circPITX1 的表达水平与放疗敏感度及预后的相关性研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年01期
页码:
27-32
栏目:
论著
出版日期:
2023-01-15

文章信息/Info

Title:
Correlation between the Expression Levels of NEK2 and CircPITX1 and Radiotherapy Sensitivity and Prognosis in Cervical Cancer
文章编号:
1671-7414(2023)01-027-06
作者:
陈 霄吴小颖安 明
(四川大学华西三亚医院妇产科,海南三亚 572000)
Author(s):
CHEN Xiao WU Xiao-ying AN Ming
(Department of Obstetrics and Gynecology,West China Sanya Hospital of Sichuan University,Hainan Sanya 572000,China)
关键词:
宫颈癌中心体相关激酶2环状RNA 配对同源结构域基因1
分类号:
R737.33;R730.43
DOI:
10.3969/j.issn.1671-7414.2023.01.006
文献标志码:
A
摘要:
目的 探讨宫颈癌组织中中心体相关激酶2(never in mitosis geneA related kinase-2,NEK2) 和环状RNA 配对同源结构域基因1(circRNA paired homology domain gene 1,circPITX1) 表达与放疗敏感度及预后的关系。方法 选取2017 年1月~ 2018 年1 月四川大学华西三亚医院接受放疗治疗的82 例宫颈癌患者为研究对象。依据放疗后病灶退缩情况评价放疗疗效,分为放疗抵抗组(n=51)和放疗敏感组(n=31)。应用免疫组织化学法(immunohistochemistry,IHCS)检测宫颈癌癌组织和癌旁组织中NEK2 蛋白表达。采用荧光实时定量PCR(real-time quantitative PCR,RT-qPCR)检测circPITX1mRNA 和NEK2mRNA 表达。统计学分析癌组织中circPITX1mRNA 和NEK2 mRNA 与放疗敏感度、临床病理特征的关系。采用 Kaplan-Meier 生存曲线分析宫颈癌患者circPITX1mRNA 和NEK2 mRNA 表达水平与患者生存预后的关系。COX 回归分析宫颈癌患者预后不良的危险因素。结果 宫颈癌癌组织中NEK2 蛋白表达阳性率[85.37%(70/82)] 高于癌旁组织[12.20%(10/82)],差异有统计学意义(χ2=87.857,P < 0.05)。癌组织中circPITX1mRNA(1.92±0.24),NEK2 mRNA 表达(2.04±0.31)高于癌旁组织(0.81±0.20,0.93±0.27)表达,差异均有统计学意义(t=32.174,24.450,均P < 0.05)。宫颈癌组织中NEK2 mRNA 与circPITX1mRNA 表达呈显著正相关(r=0.618, P < 0.05)。FIGO 分期Ⅲ A~Ⅲ B 期宫颈癌患者NEK2 mRNA(2.54±0.23),circPITX1mRNA(2.33±0.19)表达明显高于IIB 期患者(1.17±0.40,1.21±0.30)表达,差异均有统计学意义(t=19.730, 20.710,均P < 0.05)。宫颈癌放疗抵抗组NEK2 mRNA(2.39±0.38),circPITX1mRNA(2.50±0.21)均显著高于放疗敏感组(1.83±0.28,0.97±0.28),差异有统计学意义(t=7.109, 28.149, 均P < 0.05)。NEK2 mRNA[(48.78%(20/41)] 和circPITX1mRNA[54.76%(23/42)] 高表达组的三年总生存率显著低于NEK2 mRNA[90.24%(37/41)],circPITX1 mRNA 低表达组 [85.00%(34/40)],差异均有统计学意义(χ2=5.118, 4.890, 均P < 0.05);NEK2 mRNA[(26.10±3.62)个月] 和circPITX1mRNA[(25.87±3.81)个月]高表达组的平均生存时间显著短于NEK2 mRNA([ 33.25±4.09)个月]和circPITX1mRNA低表达组([ 32.02±4.02)个月],差异均有统计学意义(t=8.382, 7.140, 均P < 0.05)。FIGO 分期Ⅲ A~Ⅲ B(HR=3.754,95%CI:1.621~ 8.694),NEK2 mRNA高表达(HR=2.874,95%CI:2.504 ~ 3.497),circPITX1mRNA 高表达(HR=2.679,95%CI:2.485 ~ 3.184)是宫颈癌患者预后不良的独立危险因素(均P 均< 0.05)。结论 NEK2 和circPITX1 在宫颈癌组织中表达升高, 可成为放疗敏感度及预后预测的标志物。
Abstract:
Objective To explore the expression never in mitosis gene A-related kinase 2 (NEK2) and circRNA paired homology domain gene 1 (circPITX1) in cervical cancer tissues and their correlation with radiotherapy sensitivity and prognosis. Methods 82 patients with cervical cancer who received radiotherapy in West China Sanya Hospital of Sichuan University from January 2017 to January 2018 were selected as research object. The efficacy of radiotherapy was evaluated according to the lesion shrinkage after radiotherapy, and the patients were divided into radiotherapy resistant group (n=51) and radiotherapy sensitive group (n=31). The expression of NEK2 protein in cervical cancer tissues and adjacent tissues was detected by immunohistochemistry(iIHCS). The expression of circPITX1mRNA and NEK2 mRNA was detected by fluorescence realtime quantitative PCR(RT-qPCR). The relationship between circPITX1 mRNA and NEK2 mRNA in cancer tissue with radiosensitivity and clinicopathological characteristics was statistically analyzed. The Kaplan-Meier survival curve was used to analyze the relationship between the expression levels of circPITX1mRNA and NEK2 mRNA and the 3-year prognosis of cervical cancer patients.COX regression analysis was used to analyze the risk factors of poor prognosis in patients with cervical cancer. Results The positive rate of NEK2 protein expression in cervical cancer tissues [85.37% (70/82)] was higher than that in adjacent tissues [12.20% (10/82)], and the difference was statistically significant (χ2=87.857, P < 0.05). The expressions of circPITX1mRNA (1.92±0.24) and NEK2 mRNA (2.04±0.31) in cancer tissues were higher than those of circPITX1 mRNA (0.81±0.20) and NEK2 mRNA (0.93±0.27) paracancerous tissues, and the differences were statistically significant (t=32.174, 24.450, all P < 0.05). There was a significant positive correlation between NEK2 mRNA and CircPITX1mRNA expression in cervical cancer tissue (r=0.618, P < 0.05). The expressions of NEK2 mRNA (2.54±0.23) and circPITX1mRNA (2.33±0.19) in patients with FIGO stage IIIA ~ IIIB cervical cancer were significantly higher than those in IIB stage patients (1.17±0.40) and CircPITX1 mRNA(1.21±0.30),and the differences were statistical significance (t=19.730, 20.710, all P < 0.05). The NEK2 mRNA (2.39±0.38) and circPITX1mRNA (2.50±0.21) in the radiotherapy-resistant cervical cancer group were significantly higher than those in the radiosensitive group (1.83±0.28, 0.97±0.28), and the differences were statistically significant (t =7.109, 28.149,all P < 0.05). The 3-year overall survival rate of NEK2 mRNA [(48.78% (20/41)], circPITX1mRNA [54.76% (23/42)] high expression group was significantly lower than that of NEK2 mRNA [90.24% (37/41)], and CircPITX1mRNA low expression group [85.00% (34/40)], and the differences were statistically significant (χ2=5.118, 4.890, all P < 0.05). The mean survival time of NEK2 mRNA [(26.10±3.62) months] and circPITX1mRNA [(25.87±3.81) months] high expression group was significantly shorter than that of NEK2 mRNA [(33.25±4.09) months] and the circPITX1mRNA low expression group [(32.02±4.02) months], and the differences were statistically significant (t=8.382, 7.140,all P < 0.05). FIGO stage IIIA ~ IIIB (HR=3.754, 95%CI: 1.621 ~ 8.694), high expression of NEK2 mRNA (HR=2.874, 95%CI: 2.504 ~ 3.497), high expression of circPITX1mRNA (HR=2.679, 95%CI: 2.485 ~ 3.184) were independent risk factors for poor prognosis of cervical cancer patients (all P < 0.05). Conclusion NEK2 and circPITX1were up-regulated in cervical cancer tissues and could be used as markers for radiosensitivity and prognosis prediction.

参考文献/References:

[1] SUNDSTR?M K, ELFSTR?M K M. Advances in cervical cancer prevention: efficacy, effectiveness,elimination[J]. PLoS Medicine, 2020, 17(1): e1003035.
[2] 徐晓锋, 王纯, 卢国丰, 等. 宫颈癌患者Kruppel 样因子6, p21 蛋白表达水平与病理特征及化疗敏感性的相关性分析[J]. 现代检验医学杂志, 2020, 35(6):12-15.
XU Xiaofeng, WANG Chun, LU Guofeng, et al.Correlation analysis of KLF6 and p21 protein expression levels and pathological features and chemotherapy sensitivity in patients with cervical cancer [J]. Journal of Modern Laboratory Medicine,2020, 35(6): 12-15.
[3] ZHANG Xiaozhen, HUANG Xing, XU Jian,et al. NEK2 inhibition triggers anti-pancreatic cancer immunity by targeting PD-L1[J]. Nature Communications, 2021, 12(1): 4536.
[4] GUAN Yongchang, CAO Zhi, DU Jinghua, et al. Circular RNA circPITX1 knockdown inhibits glycolysis to enhance radiosensitivity of glioma cells by miR-329-3p/NEK2 axis[J]. Cancer Cell International, 2020, 20: 80.
[5] CHAICHIAN S, SHAFABAKHSH R, MIRHASHEMI S M, et al. Circular RNAs: A novel biomarker for cervical cancer[J]. Journal of Cellular Physiology,2020, 235(2): 718-724.
[6] LI Wei, YANG Pan, ZHONG Chucheng, et al. The circ-PITX1 promotes non-small cell lung cancer development via the miR-30e-5p/ITGA6 axis[J]. Cell Cycle (Georgetown, Tex.), 2022, 21(3): 304-321.
[7] 赵挺祺, 李时荣, 王静媛, 等. 非小细胞肺癌中LASS2/TMSG1 的表达及其临床意义[J]. 临床与实验病理学杂志, 2020, 36(3): 323-325.
ZHAO Tingqi, LI Shirong, WANG Jingyuan, et al.Expression of LASS2/TMSG1 in non-small cell lung cancer and its clinical significance [J]. Chinese Journal of Clinical and Experimental Pathology, 2020, 36(3):323-325.
[8] GUPTA S, MAHESHWARI A, PARAB P, et al.Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: A randomized controlled trial[J]. Journal of Clinical Oncology, 2018, 36(16): 1548-1555.
[9] XU Tie, ZENG Yulan, SHI Linli, et al. Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer[J]. Journal of Experimental & Clinical Cancer Research, 2020, 39(1): 183.
[10] JI Yuanyuan, MENG Man, MIAO Ye. LncRNA SNHG1 promotes progression of cervical cancer through miR-195/NEK2 axis[J]. Cancer Management and Research,2020, 12(4): 11423-11433.
[11] WAN Hao, XU Lin, ZHANG Huangbin, et al.High expression of NEK2 promotes gastric cancer progression via activating AKT signaling[J]. Journal of Physiology and Biochemistry, 2021, 77(1): 25-34.
[12] YANG Yu, ZHOU Huangdi, ZHANG Ge, et al.Targeting the canonical Wnt/β-catenin pathway in cancer radioresistance: Updates on the molecular mechanisms[J]. Journal of Cancer Research and Therapeutics, 2019, 15(2): 272-277.
[13] JUN S, JUNG Y S, SUH H N, et al. LIG4 mediates Wnt signalling-induced radioresistance[J]. Nature Communications, 2016, 7(5): 10994.
[14] 张振, 潘晴, 刘旭, 等.circRNA 与肿瘤发生的研究进展[J]. 现代检验医学杂志, 2018, 33(2): 157-159,164.
ZHANG Zhen, PAN Qing, LIU Xu, et al. Research progress of the relationship between circular RNA and tumorigenesis[J]. Journal of Modern Laboratory Medicine, 2018, 33(2): 157-159, 164.
[15] 申倩倩, 王焱, 王晓, 等. 沉默环状RNA hsa_circ_0011021 表达对宫颈癌细胞增殖迁移及侵袭的影响[J]. 西部医学, 2019, 31(9): 1339-1343.
SHEN Qianqian, WANG Yan, WANG Xiao, et al.Effect of knockdown of circular RNA hsa_circ_011021 on the proliferation, migration and invasion of cervical cancer cells[J]. Medical Journal of West China, 2019,31(9): 1339-1343.
[16] CUI Chaochu, YANG Jianbo, LI Xiao, et al.Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance[J]. Molecular Cancer, 2020, 19(1): 58.
[17] L? Xinwen, WANG Meihua, QIANG Jingli, et al.Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis[J].European Journal of Pharmacology, 2019, 863(3):172643.
[18] ZHANG Lele, HOU Chaofeng, CHEN Chen, et al. The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs [J]. Molecular Cancer, 2020,19(1):105.
[19] JI Fei, LU Yang, CHEN Shaoyun, et al. IGF2BP2-modified circular RNA circARHGAP12 promotes cervical cancer progression by interacting Ma/FOXM1 manner[J]. Cell Death Discovery, 2021, 7(1): 215.
[20] ZHAN Lan, MU Zhuang, YANG Mingchun, et al.Elevation of circ-PITX1 upregulates interleukin 17 receptor D expression via sponging miR-518a-5p and facilitates cell progression in glioma[J]. Journal of Cellular Biochemistry, 2019, 120(10): 16495-16502.
[21] HUANG Chunxian, LU Huaiwu, LI Jing, et al. SOX2 regulates radioresistance in cervical cancer via the hedgehog signaling pathway[J]. Gynecologic Oncology,2018, 151(3): 533-541.
[22] CHE Yilin, LI Yizhuo, ZHENG Fufu, et al. TRIP4 promotes tumor growth and metastasis and regulates radiosensitivity of cervical cancer by activating MAPK,PI3K/AKT, and hTERT signaling[J]. Cancer Letters,2019, 452: 1-13.

相似文献/References:

[1]田英,王双勇,赵雅,等.宫颈癌组织细胞中Numb基因表达及相关性研究[J].现代检验医学杂志,2015,30(06):42.[doi:10.3969/j.issn.1671-7414.2015.06.012]
 TIAN Ying,WANG Shuang-yong,ZHAO Ya,et al.Study on Correlation and Expression of Numb Gene in Cervical Cancer[J].Journal of Modern Laboratory Medicine,2015,30(01):42.[doi:10.3969/j.issn.1671-7414.2015.06.012]
[2]顾益凤,朱自力,史跃燕,等.血浆硫氧还蛋白还原酶水平检测对宫颈癌早期诊断的价值研究[J].现代检验医学杂志,2019,34(02):40.[doi:10.3969/j.issn.1671-7414.2019.02.011]
 GU Yi-feng,ZHU Zi-li,SHI Yue-yan,et al.Study on the Value of Plasma Thioredoxin Reductase Levelin the Early Diagnosis of Cervical Cancer[J].Journal of Modern Laboratory Medicine,2019,34(01):40.[doi:10.3969/j.issn.1671-7414.2019.02.011]
[3]陈 慎,杜明君,宋雅琴.宫颈组织HPV DNA与血清Chemerin,Leptin水平联合检测对宫颈癌早期诊断的价值分析[J].现代检验医学杂志,2019,34(03):42.[doi:10.3969/j.issn.1671-7414.2019.03.010]
 CHEN Shen,DU Ming-jun,SONG Ya-qin.Value of Combined Detection of HPV DNA and Serum Levelsof Chemerin and Leptin in Early Diagnosis of Cervical Cancer[J].Journal of Modern Laboratory Medicine,2019,34(01):42.[doi:10.3969/j.issn.1671-7414.2019.03.010]
[4]周 静,李 智,周 玉,等.宫颈癌组织中 Ep-CAM和 Ki67的表达及临床意义[J].现代检验医学杂志,2019,34(06):24.[doi:10.3969 / j.issn.1671-7414.2019.06.006]
 ZHOU Jing,LI Zhi,ZHOU Yu,et al.Expression and Clinicd Value of Ep-CAM and Ki67 in the Cervial Carcinoma Tissue[J].Journal of Modern Laboratory Medicine,2019,34(01):24.[doi:10.3969 / j.issn.1671-7414.2019.06.006]
[5]徐晓锋a,王 纯b,卢国丰a,等.宫颈癌患者 Kruppel 样因子 6,p21 蛋白表达水平与病理特征及化疗敏感性的相关性分析[J].现代检验医学杂志,2020,35(06):12.[doi:doi:10.3969/j.issn.1671-7414.2020.06.004]
 XU Xiao-feng a,WANG Chun b,LU Guo-feng a,et al.Correlation Analysis of KLF6 and p21 Protein Expression Levels andPathological Features and Chemotherapy Sensitivity in Patientswith Cervical Cancer[J].Journal of Modern Laboratory Medicine,2020,35(01):12.[doi:doi:10.3969/j.issn.1671-7414.2020.06.004]
[6]高红敏,杨红英,刘 鑫.血清中 microRNA-106b 对宫颈癌患者的早期诊断及预后预测价值[J].现代检验医学杂志,2020,35(06):85.[doi:doi:10.3969/j.issn.1671-7414.2020.06.020]
 GAO Hong-min,YANG Hong-ying,LIU Xin.Value Analysis of Serum microRNA-106b in Early Diagnosis ofCervical Cancer[J].Journal of Modern Laboratory Medicine,2020,35(01):85.[doi:doi:10.3969/j.issn.1671-7414.2020.06.020]
[7]赵白信,于慧娟,焦方杰,等.经阴道彩色多普勒超声联合血清 miR-130a,miR-425-5p 水平检测对宫颈癌的诊断效能分析[J].现代检验医学杂志,2021,36(03):43.[doi:10.3969/j.issn.1671-7414.2021.03.010]
 ZHAO Bai-xin,YU Hui-juan,JIAO Fang-jie,et al.Analysis of Diagnostic Efficacy of Transvaginal Color Doppler UltrasoundCombined with Serum miR-130a and miR-425-5p Levels in Cervical Cancer[J].Journal of Modern Laboratory Medicine,2021,36(01):43.[doi:10.3969/j.issn.1671-7414.2021.03.010]
[8]张治洋,李功娟.10株宫颈癌细胞系中MALAT1的表达及其对顺铂敏感性的影响[J].现代检验医学杂志,2021,36(05):110.[doi:10.3969/j.issn.1671-7414.2021.05.024]
 ZHANG Zhi-yang,LI Gong-juan.Expression of MALAT1 in 10 Cervical Cancer Cell Lines and Its Effect onCisplatin Sensitivity[J].Journal of Modern Laboratory Medicine,2021,36(01):110.[doi:10.3969/j.issn.1671-7414.2021.05.024]
[9]郝艳芳,刘亚荣,黄玲玲,等.miRNA-195靶向调控 CCND2和 MYB抑制宫颈癌细胞增殖、迁移的机制研究[J].现代检验医学杂志,2022,37(01):130.[doi:10.3969/j.issn.1671-7414.2022.01.026]
 HAO Yan-fang,LIU Ya-rong,HUANG Ling-ling,et al.Study on the Mechanism of miRNA-195 Targeting CCND2 and MYB to Inhibit the Proliferation and Migration of Cervical Cancer Cells[J].Journal of Modern Laboratory Medicine,2022,37(01):130.[doi:10.3969/j.issn.1671-7414.2022.01.026]
[10]方 芳,吴 玲,魏善闯,等.宫颈癌患者血清LCN2水平表达与HPV病毒载量及临床分期的相关研究[J].现代检验医学杂志,2022,37(02):80.[doi:10.3969/j.issn.1671-7414.2022.02.017]
 FANG Fang,WU Ling,WEI Shan-chuang,et al.Correlation of Expression of Serum LCN2 Level with HPV Load and Clinical Stage in Patients with Cervical Cancer[J].Journal of Modern Laboratory Medicine,2022,37(01):80.[doi:10.3969/j.issn.1671-7414.2022.02.017]

备注/Memo

备注/Memo:
基金项目:海南省自然科学基金项目(20169426)。
作者简介:陈霄(1987-),女,本科,主治医师,研究方向:妇产科疾病相关研究, E-mail:chenxiao19870352@163.com。
更新日期/Last Update: 2023-01-15