您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (11): 47-53.doi: 10.6040/j.issn.1671-7554.0.2016.133

• 临床医学 • 上一篇    下一篇

PADI2与人多种肿瘤的遗传易感性的关系

李昌1,2,张倩3,马芳4,解奇2,常晓天2   

  1. 1. 山东省滕州市中心人民医院病理科, 山东 滕州 277500;2. 山东大学附属千佛山医院医学研究中心, 山东 济南 250014;3. 北大医疗鲁中医院检验科, 山东 淄博 255400;4. 山东省创新制药有限公司, 山东 济南 250101
  • 收稿日期:2016-02-08 出版日期:2017-11-10 发布日期:2017-11-10
  • 通讯作者: 常晓天. E-mail:changxt@126.com E-mail:changxt@126.com
  • 基金资助:
    山东省卫生科技发展计划(2014GSF118135,2014WS0021,2016WS0629);国家自然科学基金面上项目(81171990)

Relationship between PADI2 and genetic susceptibility in various human tumors

LI Chang1,2, ZHANG Qian3, MA Fang4, XIE Qi2, CHANG Xiaotian2   

  1. 1. Pathological Department, Tengzhou Central People's Hosptial, Tengzhou 277500, Shandong, China;
    2. Medical Research Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    3. Clinical Laboratory, PKU Care Luzhong Hospital, Zibo 255400, Shandong, China;
    4. Shandong Chuangxin Biological Technology Company, Jinan 250101, Shandong, China
  • Received:2016-02-08 Online:2017-11-10 Published:2017-11-10

摘要: 目的 探讨肽基精氨酸脱亚氨酶(PAD)家族成员之一PADI2基因对肿瘤的遗传易感性及其在肿瘤组织和患者血液中的表达情况。 方法 采用Sequenom MassARRAY基因分型技术分析PADI2编码基因上的标签单核苷酸多态性(SNP)rs2746533、rs79395834、rs2076616和rs10788656位点与乳腺癌、宫颈癌、食管癌、胃癌、肝癌、肺癌、卵巢癌和直肠癌患者是否存在遗传易感性。采用免疫组化技术检测PADI2在乳腺癌、宫颈癌、食管癌、胃癌、肝癌、肺癌、卵巢癌、结肠癌、直肠癌和甲状腺癌组织内的表达。采用ELISA技术检测PADI2在乳腺癌、宫颈癌、食管癌、胃癌、肝癌、肺癌、卵巢癌、直肠癌患者外周血中的表达水平。 结果 Sequenom MassARRAY基因分型实验显示,PADI2基因的rs2746533、rs2076616、rs10788656位点与乳腺癌、宫颈癌、胃癌、肺癌、直肠癌发病明显相关。免疫组化实验发现,PADI2在95%的乳腺浸润性导管癌、97.5%的结肠腺癌、88%的食管癌、92.5%的肺癌和90%甲状腺乳头状癌组织高表达。除了一些间充质样细胞和内皮细胞外,PADI2在正常宫颈组织、肺组织、卵巢组织或甲状腺组织中不表达,在乳腺、结肠、食管、胃、肝和直肠正常组织的上皮细胞中低表达。ELISA实验发现PADI2在86%的肝癌、38%宫颈癌和32%胃癌患者外周血中表达水平上升2倍以上。 结论 PADI2与多种肿瘤遗传易感性相关并在多种肿瘤组织和血液中高表达,提示PADI2可能与这些肿瘤的发病有关。

关键词: 易感基因, 肿瘤, 基因分型, 肽基精氨酸脱亚氨酶2, 基因表达

Abstract: Objective To investigate the expression of peptidyl demitasse isoform 2(PADI2), a PAD family member, in various tumor tissues and the blood of patients and to investigate the correlation between PADI2 encoding gene and tumor risks. Methods Sequenom MassARRAY genotyping assay was used to determine the potential association of tag single nucleotide polymorphisms(SNPs)including rs2746533, rs79395834, rs2076616, rs10788656 in PADI2 gene to various tumor types(breast cancer, cervical cancer, esophageal cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, colon cancer, rectal cancer and thyroid cancer). Immunohistochemistry was used to determine the PADI2 expression and location in tumor tissues. ELISA was used to detect the PADI2 level in blood of the tumor 山 东 大 学 学 报 (医 学 版)55卷11期 -李昌,等.PADI2与人多种肿瘤的遗传易感性的关系 \=-patients. Results The case-control analysis showed a significant association between rs2746533, rs2076616 and rs10788656 and breast cancer, cervical carcinoma, esophageal carcinoma, gastric carcinoma, lung cancer and rectal carcinoma risks. PADI2 expression significantly increased in 95% of the patients with breast invasive ductal carcinoma, 97.5% of the patients with colonal adenocarcinoma, 88% of the patients with esophageal squamous cell carcinoma, and 92.5% of the patients with lung cancers and 90% of thyroid carcinoma papillary carcinoma samples, but not in the corresponding healthy tissues, except that in some mesenchymal cells and endothelial cells. A two-fold increase in PADI2 expression was detected in the blood of 86% of patients with liver cancer, 38% of patients with cervical carcinoma and 32% of patients with gastric carcinoma. Conclusion PADI2 has genetic susceptibility to many kinds of tumor and is highly expressed in various tumor tissues and blood of the patients. The finding suggests an important role for PADI2 in tumorigenesis.

Key words: Susceptibility gene, Tumor, Gene expression, Peptidyl deiminase isoform 2, Genotype

中图分类号: 

  • R394.5
[1] Wesche J, Kuhn S, Kessler BM, et al. Protein arginine methylation: a prominent modification and its demethylation[J]. Cell Mol Life Sci, 2017, 74(18): 3305-3315.
[2] Tu R, Grover HM, Kotra LP. Peptidyl arginine deiminases and neurodegenerative diseases[J]. Curr Med Chem, 2016, 23(2):104-114.
[3] Mohanan S, Cherrington BD, Horibata S, et al. Potential role of peptidylarginine deiminase enzymes and protein citrullination in cancer pathogenesis[J]. Biochem Res Int, 2012: 895343. doi:10.1155/2012/895343.
[4] McElwee JL, Mohanan S, Griffith OL, et al. Identification of PADI2 as a potential breast cancer biomarker and therapeutic target[J]. BMC Cancer, 2012, 12: 500. doi: 10.1186/1471-2407-12-500.
[5] Cherrington BD, Morency E, Struble AM, et al. Potential role for peptidylarginine deiminase 2(PAD2)in citrullination of canine mammary epithelial cell histones[J]. PLoS One, 2010, 5(7): e11768. doi: 10.1371/journal.pone.0011768.
[6] Cherrington BD, Mohanan S, Diep AN, et al. Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours[J]. J Comp Pathol, 2012, 147(2-3): 139-146.
[7] McElwee JL, Mohanan S, Horibata S, et al. PAD2 overexpression in transgenic mice promotes spontaneous skin neoplasia[J]. Cancer Res, 2014, 74(21):6306-6317.
[8] Briggs DJ, Skeeles JK. An enzyme-linked immunosorbent assay for detecting antibodies to Pasteurella multocida in chickens[J]. Avian Dis, 1984, 28(1):208-215.
[9] Chang X, Xia Y, Pan J, et al. PADI2 is significantly associated with rheumatoid arthritis[J]. PLoS One, 2013, 8(12): e81259. doi: 10.1371/journal.pone.0081259.
[10] Shangkuan WC, Lin HC, Chang YT, et al. Risk analysis of colorectal cancer incidence by gene expression analysis[J]. PeerJ, 2017, 5: e3003. doi: 10.7717/peerj.3003.
[11] Cherrington BD, Zhang X, McElwee JL, et al. Potential role for PAD2 in gene regulation in breast cancer cells[J]. PLoS One, 2012, 7(7): e41242. doi: 10.1371/journal.pone.0041242.
[12] Bhattacharya SK, Crabb JS, Bonilha VL, et al. Proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis[J]. Invest Ophthalmol Vis Sci, 2006, 47(6):2508-2514.
[13] McElwee JL, Mohanan S, Horibata S, et al. PAD2 overexpression in transgenic mice promotes spontaneous skin neoplasia[J]. Cancer Res, 2014, 74(21):6306-6317.
[14] Cantarino N, Musulen E, Valero V, et al. Downregulation of the deiminase PADI2 is an early event in colorectal carcinogenesis and indicates poor prognosis[J]. Mol Cancer Res, 2016, 14(9):841-848.
[15] Wang H, Xu B, Zhang X, et al. PADI2 gene confers susceptibility to breast cancer and plays tumorigenic role via ACSL4, BINC3 and CA9 signaling[J]. Cancer Cell Int, 2016, 16:61. doi: 10.1186/s12935-016-0335-0.
[16] Jiang Z, Cui Y, Wang L, et al. Investigating citrullinated proteins in tumour cell lines[J]. World J Surg Oncol, 2013, 11: 260. doi: 10.1186/1477-7819-11-260.
[17] Chang X, Fang K. PADI4 and tumourigenesis[J]. Cancer Cell Int, 2010, 10:7. doi: 10.1186/1475-2867-10-7.
[18] Slack JL, Causey CP, Thompson PR. Protein arginine deiminase 4: a target for an epigenetic cancer therapy[J]. Cell Mol Life Sci, 2011, 68(4):709-720.
[19] Ying S, Dong S, Kawada A, et al. Transcriptional regulation of peptidylarginine deiminase expression in human keratinocytes[J]. J Dermatol Sci, 2009, 53(1): 2-9.
[1] 王伟 王沂峰 张岭梅 林琼燕 黄菊. 人卵巢癌OVCAR3细胞系中侧群细胞的分离及其成瘤性、侵袭性的实验研究[J]. 山东大学学报(医学版), 2209, 47(6): 8-11.
[2] 张士宝 刘庆勇 阮喜云 陈杰 张建军 李宗武 杨广笑 王全颖. NT4-SAC-HA2-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[3] 李波波 李道堂 刘曙光 王兴武. 食管癌患者血清中DKK-1的表达[J]. 山东大学学报(医学版), 2209, 47(6): 58-61.
[4] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[5] 黄方 康瑞 吴春林. VEGFC、NF-κBp65及Survivin在鼻咽癌中的表达及临床意义[J]. 山东大学学报(医学版), 2209, 47(6): 83-.
[6] 孙文雄,吴日超,郑贤静,李丽, 张友忠. 宫颈血管周上皮样细胞肿瘤1例[J]. 山东大学学报 (医学版), 2022, 60(9): 125-128.
[7] 吴瑞芳,李长忠. 女性生育力保护的现状与进展[J]. 山东大学学报 (医学版), 2022, 60(9): 1-7.
[8] 王丽慧,高敏,孔北华. 子宫血管肉瘤2例报告并文献复习[J]. 山东大学学报 (医学版), 2022, 60(9): 108-112.
[9] 张艺馨,赵玉立,封丽. 超声特征及术前CA-125联合对51例卵巢交界性及Ⅰ期恶性肿瘤的鉴别诊断[J]. 山东大学学报 (医学版), 2022, 60(7): 104-109.
[10] 李琳琳,王凯. 基于生物信息学预测肝细胞癌预后基因[J]. 山东大学学报 (医学版), 2022, 60(5): 50-58.
[11] 宋钰峰,宁豪,姚志刚,吴海虎,刘非凡,吕家驹. 肾上腺海绵状血管瘤临床及影像特征[J]. 山东大学学报 (医学版), 2022, 60(2): 37-42.
[12] 程传龙,杨淑霞,佘凯丽,房启迪,韩闯,刘盈,崔峰,李秀君. 淄博市2018年恶性肿瘤的流行特征及影响因素[J]. 山东大学学报 (医学版), 2022, 60(2): 102-108.
[13] 亓梦雨,周敏然,孙洺山,李世洁,陈春燕. T大颗粒淋巴细胞白血病合并原发性骨髓纤维化1例[J]. 山东大学学报 (医学版), 2022, 60(2): 118-120.
[14] 孙树洋,张志愿. 基于肿瘤临床前模型建立头颈癌新型药物基因组学的必要性及展望[J]. 山东大学学报 (医学版), 2021, 59(9): 57-63.
[15] 王传新. 肿瘤液体活检[J]. 山东大学学报 (医学版), 2021, 59(9): 64-71.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 张杰,李振华,孙晋浩,暴丽华,刘岳鹏. 恒定磁场对Schwann细胞氧化损伤的保护作用[J]. 山东大学学报(医学版), 2007, 45(3): 229 -232 .
[2] 郑敏,郝跃伟,刘雪平,赵婷婷. 血小板膜糖蛋白Ibα基因HPA-2、Kozak序列多态性与脑梗死的相关性研究[J]. 山东大学学报(医学版), 2008, 46(3): 292 -295 .
[3] 方英立,马玉燕,刘锡梅,周文 . 急诊剖宫产患者围手术期替硝唑合理应用[J]. 山东大学学报(医学版), 2007, 45(10): 995 .
[4] 姜红菊,李润智,王营,徐冬梅,张梅,张运,李继福 . 冠状动脉粥样硬化斑块形态及介入治疗与MMP-9的关系[J]. 山东大学学报(医学版), 2008, 46(10): 966 -970 .
[5] 李明霞,王学禹 . 儿童急性播散性脑脊髓炎31例临床与MRI特点[J]. 山东大学学报(医学版), 2008, 46(8): 828 -830 .
[6] . Graves病131治疗后1年内早发甲减影响因素分析[J]. 山东大学学报(医学版), 2009, 47(9): 5 -6 .
[7] 牛瑞,刘波,邵明举,王伟 . 非小细胞肺癌区域淋巴结中肺组织特异性基因的表达与预后的关系[J]. 山东大学学报(医学版), 2007, 45(9): 884 -885 .
[8] 王术芹,齐 峰,吴剑波,孙宝柱. 罗哌卡因对大鼠离体主动脉收缩作用的钙离子调节机制[J]. 山东大学学报(医学版), 2008, 46(8): 773 -776 .
[9] 滕学仁,赵永生,胡光亮,周伦,李建民 . 两种方法保存同种异体髌腱移植重建膝关节交叉韧带的光镜电镜观察[J]. 山东大学学报(医学版), 2008, 46(10): 945 -950 .
[10] 焦芳芳,刘世青,李飞,李长生,王琴,孙青,鹿伟 . 化瘀理肺方对大鼠肺间质纤维化时Smad7和TGF-β表达的影响[J]. 山东大学学报(医学版), 2007, 45(10): 1054 -1058 .