Pannexin-1在垂体腺瘤中的表达及意义

Expression and roles of Pannexin-1 in pituitary adenoma

目的探讨Pannexin-1在各亚型垂体腺瘤中的表达以及其与激素水平、肿瘤侵袭性和增殖能力之间的关系。方法根据Gene Expression Omnibus(GEO)数据库分析Pannexin-1在垂体腺瘤各亚型中的表达情况。此外收集垂体腺瘤56例及正常垂体4例,依据术前激素分泌水平、术后病理诊断和临床表现确定垂体腺瘤类型,根据术中所见、影像学表现以及病检结果确定肿瘤侵袭性分级(Knosp分级),根据Ki-67指数判断肿瘤增殖能力。56例垂体腺瘤中,无功能垂体腺瘤(nonfunctional pituitary adenoma,NFPA)28例,侵袭性和非侵袭性各占14例;生长激素腺瘤(growth hormone pituitary adenoma,GH-PA)16例,侵袭性和非侵袭性各占8例;催乳素腺瘤(prolactin pituitary adenoma,PRL-PA)12例,侵袭性和非侵袭性各占6例。用反转录-定量PCR(reverse transcription-quantitative PCR,RT-qPCR)和免疫组织化学技术分别测定Pannexin-1 mRNA和Pannexin-1蛋白的表达。结果根据GEO数据库分析,相较于正常垂体(normal pituitary,NP),Pannexin-1在各亚型垂体腺瘤中表达均上调(P<0.05)。根据实验结果,Pannexin-1蛋白和mRNA在NFPA、GH-PA和PRL-PA患者组织中均有表达。与非侵袭性垂体腺瘤比较,侵袭性垂体腺瘤中Pannexin-1的表达更高(P<0.05)。Ki-67指数≥3%组和Ki-67指数<3%组比较,Pannexin-1 mRNA表达量差异无统计学意义(P>0.05)。GH-PA组Pannexin-1 mRNA的表达量与其术前的生长激素水平无相关性(r=0.24,P=0.16)。PRL-PA组Pannexin-1 mRNA的表达量与其术前的催乳素水平无相关性(r=0.37,P=0.21)。结论Pannexin-1的表达高低与垂体腺瘤的侵袭性有关,侵袭性垂体腺瘤中Pannexin-1表达增高。Pannexin-1的表达与激素水平和肿瘤的增殖能力(Ki-67指数)无关。

Objective To investigate the expression of Pannexin-1 in pituitary adenoma and its relationship with hormone levels,tumor invasion and proliferative ability.Methods The expression of Pannexin-1 in each subtype of pituitary adenoma was analyzed according to Gene Expression omnibus(GEO)database.Fifty-six cases of pituitary adenoma and 4 samples of normal pituitary were collected,and the type of pituitary adenoma was determined according to the preoperative hormone secretion level,postoperative pathological diagnosis and clinical manifestations.According to the intraoperative imaging findings and disease examination results,the tumor invasion grade(Knosp grade)was determined.According to the Ki-67 index,the tumor proliferation ability was determined.Among the 56 pituitary adenoma cases,28 cases were non-functional pituitary adenoma(NFPA),with 14 cases invasive and 14 cases non-invasive,16 cases were growth hormone pituitary adenoma(GH-PA),with 8 invasive and 8 non-invasive,and 12 cases were prolactin pituitary adenoma(PRL-PA),with 6 invasive and 6 non-invasive.Reverse transcription-quantitative PCR(RT-qPCR)and immunohistochemistry were used to determine the expression of Pannexin-1 mRNA and protein.Results According to GEO database analysis,Pannexin-1 expression was upregulated in all subtypes of pituitary adenomas compared to normal pituitary(P<0.05).According to the experimental results of the 56 pituitary adenoma cases,Pannexin-1 was expressed in all NFPA,GH-PA and PRL-PA cases.Compared with the non-invasive pituitary adenoma,the expression of Pannexin-1 was higher in the invasive pituitary adenoma(P<0.05).There was no significant difference in the expression of Pannexin-1 between the Ki-67 index≥3%group and the Ki-67 index<3%group(P>0.05).There was no correlation between Pannexin-1 mRNA expression and preoperative growth hormone level in GH-PA(r=0.24,P=0.16)and between Pannexin-1 mRNA expression and preoperative prolactin level in PRL-PA(r=0.37,P=0.21).Conclusions The level of Pannexin-1 expression was correlated with the aggressiveness of pituitary adenoma,and was significantly increased in invasive pituitary adenoma.The expression of Pannexin-1 was not related to hormone levels and tumor proliferation ability(Ki-67 index).