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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

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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
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