蛋白激酶WEE1在胃癌组织中的表达及其临床意义

李菁, 金玉, 李启阳, 许英卓, 刘超, 肖建英

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (6) : 680-684.

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (6) : 680-684. DOI: 10.13418/j.issn.1001-165x.2020.06.011
实验研究

蛋白激酶WEE1在胃癌组织中的表达及其临床意义

  • 李菁1, 金玉2, 李启阳1, 许英卓1, 刘超2, 肖建英1
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Expression of protein kinase WEE1 in gastric cancer tissue and its clinical significance

  • LI Jing1, JIN Yu2, LI Qi-yang1, XU Ying-zhuo1, LIU Chao2, XIAO Jian-ying1
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摘要

目的 探讨蛋白激酶WEE1在胃癌组织中的表达及其与胃癌临床指标的相关性,并阐述其在胃癌发生发展中的作用。  方法 使用Oncomine数据库分析WEE1在胃腺癌和胃黏膜组织中的表达差异。选取100例胃腺癌和80例癌旁组织标本,通过免疫组织化学法和组织芯片技术检测WEE1蛋白在胃癌和癌旁组织中的表达水平。对免疫组织化学结果中染色的比例以及染色程度进行半定量分析,对半定量分析结果与胃癌临床指标进行相关性分析。使用RT-PCR和Western blotting检测WEE1在胃癌和癌旁组织中的mRNA和蛋白表达水平。  结果 WEE1在100例胃癌患者中的阳性率为86%,高表达86例,低表达14例。通过Oncomine数据库分析,蛋白激酶WEE1在胃腺癌中的表达明显高于胃黏膜组织中的表达(P<0.01)。免疫组化、RT-PCR和Western blotting均显示,WEE1在胃癌组织中的表达明显高于癌旁组织(P<0.01);免疫组化还显示WEE1的表达量随着胃癌组织分期的增加而增加(P<0.01)。  结论 蛋白激酶WEE1在胃癌组织中高表达,提示其可作为胃癌治疗靶点之一。

Abstract

Objective To investigate the expression of protein kinase WEE1 in gastric cancer tissues and the association between its protein expression and clinical indicators of patients with gastric cancer, and to clarify its role in the occurrence and development of gastric cancer. Methods The Oncomine database was used to analyze the differential expression of WEE1 in gastric adenocarcinoma and gastric mucosa. Tissue microarray and immunohistochemistry were used to detect the expression of WEE1 protein using 100 cases of gastric adenocarcinoma and 80 cases of adjacent tissues. The proportion of staining in immunohistochemistry and the degree of staining were semi-quantitatively analyzed, and the correlation between semi-quantitative analysis and clinical indexes of gastric cancer patients was relevance analyzed. Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) and Western blotting were used to detect the mRNA and protein expression of WEE1 in gastric cancer cells and gastric mucosa cells. Results The positive rate of WEE1 in gastric cancer tissues was 86%, of which 14 cases were low expression and 86 cases were high expression of the 100 patients. Oncomine database analysis showed that the expression of WEE1 mRNA in mixed gastric adenocarcinoma was higher than that in gastric mucosa (P<0.01). The results of immunohistochemistry, RT-PCR and Western blotting showed that the expression of WEE1 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.01). Moreover, the immunohistochemistry showed that the protein expression of WEE1 increased with the increasing clinical stage of gastric cancer (P<0.01).  Conclusions  Protein kinase WEE1 is highly expressed in gastric cancer tissues, suggesting that it may act as one of the therapeutic targets of gastric cancer.

关键词

蛋白激酶WEE1 /  胃癌 /  免疫组织化学 /  组织芯片 /  免疫印迹 /  逆转录-聚合酶链反应

Key words

Protein kinase WEE1 /  Gastric cancer /  Immunohistochemistry /  Tissue microarray /   / Western blotting /   /   / RT-PCR

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导出引用
李菁, 金玉, 李启阳, 许英卓, 刘超, 肖建英. 蛋白激酶WEE1在胃癌组织中的表达及其临床意义[J]. 中国临床解剖学杂志. 2020, 38(6): 680-684 https://doi.org/10.13418/j.issn.1001-165x.2020.06.011
LI Jing, JIN Yu, LI Qi-yang, XU Ying-zhuo, LIU Chao, XIAO Jian-ying. Expression of protein kinase WEE1 in gastric cancer tissue and its clinical significance[J]. Chinese Journal of Clinical Anatomy. 2020, 38(6): 680-684 https://doi.org/10.13418/j.issn.1001-165x.2020.06.011
中图分类号:      R735.2   

参考文献

[1]  Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. 
[2]  陈昌望, 王璋, 周玲, 等. FZD10在胃癌中的表达以及对胃癌细胞的影响[J]. 海南医学院学报, 2019, 25(11): 853-857.
[3]  Van Cutsem E, Sagaert X, Topal B, et al. Gastric cancer[J]. Lancet, 2016, 388(10060): 2654-2664. 
[4]  Lee JH, Sung JY, Choi EK et al. C/EBPβ is a transcriptional regulator of Wee1 at the G2/M phase of the cell cycle[J]. Cells, 2019, 8(2): 145-165.
[5]  孟海, 杜观祥, 朱利玲, 等. WEE1在胃癌组织中的表达及对患者预后的影响[J]. 实用肿瘤学杂志, 2019, 33 (3): 239-243. 
[6]  Wright G, Golubeva V, Remsing Rix LL, et al. Dual targeting of WEE1 and PLK1 by AZD1775 elicits single agent cellular anticancer activity[J]. ACS Chem Biol, 2017, 12(7): 1883-1892. 
[7]  Mueller S, Haas-Kogan DA. WEE1 kinase as a target for cancer therapy[J]. J Clin Oncol, 2015, 33 (30): 3485-3487. 
[8]  Geenen JJJ, Schellens JHM. Molecular pathways: targeting the protein kinase wee1 in cancer[J]. Clin Cancer Res, 2017, 23 (16): 4540-4544. 
[9] Kim HY,Cho Y, Kang H, et al. Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer[J]. Oncotarget, 2016, 7(31): 49902-49916. 
[10]Bi SN, Wei QR, Zhao ZJ, et al. Wee1 inhibitor AZD1775 effectively inhibits the malignant phenotypes of esophageal squamous cell carcinoma in vitro and in vivo[J]. Front Pharmacol, 2019, 2(10): 864-879. 
[11]Yuan ML, Li P, Xing ZH, et al. Inhibition of WEE1 suppresses the tumor growth in laryngeal squamous cell carcinoma[J]. Front Pharmacol, 2018, 28(9): 1041-1050. 

[12]Liu WZ, Zeng XY, Yin YP, et al. Targeting the WEE1 kinase strengthens the antitumor activity of imatinib via promoting KIT autophagic degradation in gastrointestinal stromal tumors[J]. Gastric Cancer, 2020, 23(1): 39-51.    

[13] Chen DS, Lin X, Gao J, et al. Wee1 inhibitor AZD1775 combined with cisplatin potentiates anticancer activity against gastric cancer by increasing DNA damage and cell apoptosis[J]. Biomed Res Int, 2018, 5813292-5813301. 
[14] 王唯斯, 梅雯, 孙美涛, 等. 基于Oncomine和TCGA数据挖掘分析MTERF2在胰腺癌中的表达及临床意义[J]. 生物技术通讯, 2019, 30(2): 163-169. 
[15] Cho JY, Lim JY, Cheong JH, et al. Gene expression signature-based prognostic risk score in gastric cancer[J]. Clin Cancer Res, 2011, 17(7): 1850-1857. 
[16] Liu C, Ren LL, Wang YZ, et al. The interaction between RACK1 and WEE1 regulates the growth of gastric cancer cell line HGC27[J]. Oncol Lett, 2017, 14 (4): 4784-4792. 
[17] Washington K, 7th edition of the AJCC cancer staging manual: stomach[J]. Ann Surg Oncol, 2010, 17(12):3077-3079. 
[18] 穆天驰, 刘超, 富帅, 等. 基础转录激活因子1蛋白在胃癌组织中的表达及其临床意义[J]. 吉林大学学报: 医学版, 2019, 45(1): 94-99. 
[19] 金玉. 蛋白激酶WEE1和钙调蛋白激酶CAMK1G对胃癌增殖迁移影响[D].锦州: 锦州医科大学, 2019.
[20] D'Errico M, de Rinaldis E, Blasi MF, et al. Genome-wide expression profile of sporadic gastric cancers with microsatellite instability[J]. Eur J Cancer, 2009, 45(3): 461-469. 
[21] Wang XM, Li QY, Ren LL, et al. Effects of MCRS1 on proliferation, migration, invasion, and epithelial mesenchymal transition of gastric cancer cells by interacting with Pkmyt1 protein kinase [J]. Cell Signal, 2019, 59: 171-181. 
[22] 王馨梦, 李启阳, 刘超等. 微球蛋白1对胃癌细胞侵袭和迁移的影响及其机制[J]. 吉林大学学报: 医学版, 2019, 45(2): 42-48, 262.

基金

国家自然资金资助课题(81270698,31371173,81401199);辽宁省科技厅科学技术计划项目资助课题(2015020697);辽宁省教育厅高等学校创新人才项目资助课题(LR2016075)

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