吴秀娟,关长群,丁媛,普雄明,康晓静
WU Xiu-juan,GUAN Chang-qun,DING Yuan,PU Xiong-ming,KANG Xiao-jing

• 1:新疆维吾尔自治区人民医院皮肤性病科

摘要(Abstract)：

目的探讨卡波西肉瘤组织中磷脂酰肌醇-3激酶调节亚基2(phosphoinositol-3kinase regulatory subunit 2,PIK3R2)表达与卡波西肉瘤临床特征的关系。方法 30例维吾尔族卡波西肉瘤患者的卡波西肉瘤组织为卡波西肉瘤组,24例健康者手术切除的眼睑、包皮等正常皮肤组织为对照组,2组采用免疫组织化学法检测PIK3R2蛋白阳性表达率,采用实时荧光定量PCR法检测PIK3R2mRNA表达水平,分析PIK3R2表达与卡波西肉瘤组性别、年龄、病理分期、皮损面积及HIV感染的关系。结果卡波西肉瘤组PIK3R2蛋白阳性表达率(60%)和PIK3R2 mRNA表达水平(2.92±0.56)高于对照组(25%、1.24±0.82)(P<0.05);卡波西肉瘤组PIK3R2mRNA和蛋白阳性表达率在斑片期(2.37±0.20、33.3%)、斑块期(2.83±0.54、71.4%)和结节期(3.56±0.23、81.8%)比较差异均有统计学意义(P<0.05),在性别、年龄、皮损面积、HIV感染及人疱疹病毒-8型感染情况上差异无统计学意义(P>0.05);卡波西肉瘤组PIK3R2mRNA表达水平和蛋白阳性表达率与病理分期均呈正相关(r=0.897,P<0.001;r=0.437,P=0.016)。结论PIK3R2在卡波西肉瘤组织中高表达,PIK3R2 mRNA表达水平和蛋白表达在斑片期、斑块期、结节期呈递增趋势,PIK3R2有可能成为卡波西肉瘤的分子生物诊断标志物之一。
Objective To explore the relationship of the expressions of phosphoinositol-3 kinase regulatory subunit 2(PIK3 R2)protein and mRNA in Kaposi's sarcoma tissue with the clinical features of Kaposi's sarcoma.Methods The positive rate of PIK3 R2 protein was detected by immunohistochemical staining and PIK3 R2 mRNA expression was detected by real-time quantitative PCR method in Kaposi's sarcoma tissue from 30 Uygur patients with Kaposi's sarcoma(Kaposi's sarcoma group)and the normal skin such as eyelid and wrapping surgically removed from 24 healthy controls(control group).The relationships of PIK3 R2 expression with the gender,age,pathological staging,lesion area and HIV infection were analyzed.Results The positive rate of PIK3 R2 protein(60%)and the level of PIK3 R2 mRNA(2.92±0.56)in Kaposi's sarcoma group were significantly higher than those in control group(25%,1.24±0.82)(P<0.05).The level of PIK3 R2 mRNA and the positive rate of PIK3 R2 protein showed significant differences in the patch stage(2.37±0.20,33.3%),plaque stage(2.83±0.54,71.4%)and nodule stage(3.56±0.23,81.8%)(P<0.05),and showed no significance difference in the gender,age,skin lesion area,HIV infection and human herpes virus-8 infection(P>0.05)in Kaposi's sarcoma group.The level of PIK3 R2 mRNA and the positive rate of PIK3 R2 protein were positively correlated with the pathological staging in Kaposi's sarcoma group(r=0.897,P<0.001;r=0.437,P=0.016).Conclusion PIK3 R2 is highly expressed in Kaposi's sarcoma tissue,showing an increasing trend in the patch,plaque and nodule stages,and would be an important molecular biological diagnostic index.

关键词(KeyWords)： 卡波西肉瘤;磷脂酰肌醇-3激酶调节亚基2;病理演变
Kaposi's sarcoma;phosphoinositol-3kinase regulatory subunit 2;pathological development

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81660454)

作者(Author): 吴秀娟,关长群,丁媛,普雄明,康晓静
WU Xiu-juan,GUAN Chang-qun,DING Yuan,PU Xiong-ming,KANG Xiao-jing

参考文献(References)：

• [1]WANG H W,TROTTER M W,LAGOS D,et al.Kaposi sarcoma herpes virus induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma[J].Nat Genet,2004,36(7):687-693.
• [2]VILLANUEVA A,LLOVET J M.Targeted therapies for hepatocellular carcinoma[J].Gastroenterology,2011,140(5):1410-1426.
• [3]CORTS I,SNCHEZ-RUZ J,ZULUAGA S,et al.p85βphosphoinositide 3-kinase subunit regulates tumor progression[J].PNAS,2012,109(28):11318-11323.
• [4]WU X J,PU X M,ZHAO Z F,et al.The expression profiles of microRNAs in Kaposis sarcoma[J].Tumor Biol,2015,36(1):437-446.
• [5]HUANG T H,CHU T Y.Repression of miR-126 and upregulation of adrenomedullin in the stromal endothelium by cancer-stromal cross talks confers angiogenesis of cervical cancer[J].Oncogene,2014,33(28):3636-3647.
• [6]LI X,SHEN Y,ICHIKAWA H,et al.Regulation of miRNA expression by Src and contact normalization:effects on nonanchored cell growth and migration[J].Oncogene,2009,28(48):4272-4283.
• [7]FISH J E,SANTORO M M,MORTON S U,et al.MiR-126regulates angiogenic signaling and vascular integrity[J].Dev Cell,2008,15(2):272-284.
• [8]吴秀娟,丁媛,赵宗峰,等.微小RNA-126对卡波西肉瘤细胞迁移和侵袭能力的影响[J].中华实用诊断与治疗杂志,2017,31(1):26-28.
• [9]张丹丹,李庆林.PI3K/Akt/mTOR信号通路与肿瘤[J].安徽医药,2012,16(3):281-283.
• [10]PENG W,CHEN J Q,LIU C,et al.Loss of PTEN promotes resistance to T cell-mediated immunotherapy[J].Cancer Discov,2016,6(2):202-216.
• [11]DU C,LV Z,CAO L,et al.MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6and PIK3R2[J].J Transl Med,2014,12(1):259-270.
• [12]ACKAH E,YU J,ZOELLNER S,et al.Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis[J].J Clin Invest,2005,115(8):2119-2127.
• [13]CHEN J,SOMANATH P R,RAZORENOVA O,et al.Akt1regulates pathological angiogenesis,vascular maturation and permeability in vivo[J].Nat Med,2005,11(11):1188-1196.
• [14]DU C,LV Z,CAO L,et al.MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6and PIK3R2[J].J Transl Med,2014,12:259.
• [15]NIE Z C,WENG W H,SHANG Y S,et al.MicroRNA-126is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109cell via PI3K/Akt signaling pathway[J].Int J Clin Exp Pathol,2015,8(5):4745-4754.
• [16]张春梅,刘红玲.PI3K-Akt-mTOR信号通路在后发性白内障中作用的研究进展[J].中华实用诊断与治疗杂志,2017,31(3):297-299.