垂体腺瘤患者缺氧诱导因子-1α与线粒体相关基因的相关性及肿瘤侵袭和复发的影响因素研究  

Correlation of HIF-1α and Mitochondrial Related Genes and Influencing Factors of Tumor Invasion and Recurrence in Patients with Pituitary Adenoma

作　　者：张欢[1] 石文健[1] 刘永亮[1] 李景武[2] 张于[3] 董桂兰[4] 董伟[1] ZHANG Huan;SHI Wenjian;LIU Yongliang;LI Jingwu;ZHANG Yu;DONG Guilan;DONG Wei(Department of Neurosurgery,Tangshan People's Hospital,Tangshan 063000,China;Department of Tumor Surgery,Tangshan People's Hospital,Tangshan 063000,China;Department of Intensive Care Medicine,Tangshan People's Hospital,Tangshan 063000,China;Department of Oncology,Tangshan People's Hospital,Tangshan 063000,China)

机构地区：[1]河北省唐山市人民医院神经外科,063000 [2]河北省唐山市人民医院肿瘤外科,063000 [3]河北省唐山市人民医院重症医学科,063000 [4]河北省唐山市人民医院肿瘤内科,063000

出　　处：《实用心脑肺血管病杂志》2021年第11期58-62,共5页Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease

基　　金：河北省自然科学基金精准医学联合基金细化项目(H2020105017)。

摘　　要：背景线粒体功能对于肿瘤细胞的发育至关重要,线粒体功能障碍会导致酶功能异常,从而增加缺氧诱导因子(HIF)-1ɑ的稳定性,使细胞能量代谢从氧化转为糖酵解。改变的能量代谢不仅可为肿瘤细胞提供腺嘌呤核苷三磷酸,还会产生必需的代谢中间体,以促进细胞增殖,增强其侵袭性和化学抗性。目的探讨垂体腺瘤患者HIF-1α与线粒体相关基因[溶酶体相关膜蛋白1(LAMP1)、线粒体内膜融合蛋白1(OPA1)及线粒体外膜转位酶20(TOMM20)]的相关性及肿瘤侵袭和复发的影响因素。方法选取2016—2018年在唐山市人民医院接受内镜经蝶手术治疗的84例垂体腺瘤患者作为研究对象,肿瘤侵袭性:无(Knosp分级Ⅰ~Ⅱ级)38例,有(Knosp分级Ⅲ~Ⅳ级)46例;随访27~69个月,复发22例(26.2%)。通过荧光定量反转录聚合酶链式反应(RT-PCR)检测患者的HIF-1α及LAMP1、OPA1、TOMM20 mRNA相对表达量。HIF-1αmRNA相对表达量与LAMP1、OPA1及TOMM20的mRNA相对表达量的相关性分析采用Pearson相关分析。采用多因素Logistic回归分析探讨垂体腺瘤患者肿瘤侵袭和复发的影响因素。结果 Pearson相关分析结果显示,垂体腺瘤患者HIF-1αmRNA相对表达量与LAMP1、OPA1及TOMM20的mRNA相对表达量均呈正相关(r值分别为0.814、0.600、0.771,P值均<0.001)。与无侵袭性垂体腺瘤患者相比,侵袭性垂体腺瘤患者的肿瘤体积较大,Ki-67增殖指数、海绵窦受压发生率、复发率、HIF-1αmRNA相对表达量较高(P <0.05)。与未复发的垂体腺瘤患者相比,复发的垂体腺瘤患者Ki-67增殖指数、侵袭性肿瘤者占比、海绵窦受压发生率、TOMM20 mRNA相对表达量较高(P <0.05)。多因素Logistic回归分析结果显示,肿瘤体积[OR=1.179,95%CI(1.070,1.300)]、海绵窦受压[OR=23.772,95%CI(5.477,103.175)]、HIF-1αmRNA相对表达量[OR=1.018,95%CI(1.003,1.033)]是垂体腺瘤患者肿瘤侵袭的独立影响因素(P <0.05);TOMM20mRNA相对表达量[OR=1.08Background Functional mitochondria are essential for the development of tumor cells, and mitochondrial dysfunction can lead to abnormal enzymes function with consequent stabilization of hypoxiainducible factor-1α(HIF-1α) which causes a shift in energy metabolism from oxidative to glycolytic. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generates essential metabolic intermediates to support cell proliferation, invasiveness, and chemoresistance. Objective To discuss the relationships of HIF-1αand lysosomal associated membrane protein 1(LAMP1),optic atrophy 1(OPA1), translocase of outer mitochondrial membrane 20(TOMM20) and influencing factors of tumor invasion and recurrence in patients with pituitary adenoma. Methods A total of 84 patients with pituitary adenoma were enrolled by transsphenoidectomy in Tangshan People’s Hospital from 2016 to 2018, including 38 cases with tumor invasive(Knosp grade Ⅰ-Ⅱ) and 46 cases without tumor invasive(Knosp grade Ⅲ-Ⅳ). Followed up for 27-69 months, 22 cases(26.2%) were recurrence. Reverse transcription polymerase chain reaction(RT-PCR) was measured to detect mRNA relative expression quantity of HIF-1α, LAMP1, OPA1 and TOMM20 of patients with pituitary adenoma. Pearson correlation analysis was used to analyse the correlation among these indexes. Multivariate Logistic regression analysis was used to explore the influencing factors of tumor invasion and recurrence in patients with pituitary adenoma. Results Pearson correlation analysis showed that the mRNA relative expression quantity of HIF-1α was positively correlated with mRNA relative expression quantity of LAMP1, OPA1, TOMM20 of patients with pituitary adenoma(r value was 0.814, 0.600, 0.771, respectively, all P value < 0.001). Compared to pituitary adenoma patients without tumor invasive, patients with tumor invasive had larger tumor size, and higher Ki-67 proliferation index, incidence of cavernous sinus compression, recurrence rate, mRNA relative expressio

关 键 词：垂体腺瘤 低氧诱导因子-1Α 线粒体 复发 侵袭 

分 类 号：R736.4[医药卫生—肿瘤]