内源性反转录病毒-H长末端重复关联蛋白2在骨肉瘤组织的表达及其临床意义  

Expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 in osteosarcoma and its clinical significance

作　　者：窦浚峰[1] 严磊 张景义[1] 王少华[2] 周宇[2] 封青川[3] 海国栋[1] Dou Junfeng;Yan Lei;Zhang Jingyi;Wang Shaohua;Zhou Yu;Feng Qingchuan;Hai Guodong(Department of Bone Oncology and Orthopedics,Zhengzhou Orthopedic Hospital,Zhengzhou 450052,China;Department of Arthropology,Zhengzhou Orthopedic Hospital,Zhengzhou 450052,China;Department of Medical Genetics and Cell Biology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州市骨科医院骨肿瘤骨病科,郑州450052 [2]郑州市骨科医院关节病科,郑州450052 [3]郑州大学基础医学院医学遗传学与细胞生物学系,郑州450000

出　　处：《中华实验外科杂志》2024年第11期2464-2468,共5页Chinese Journal of Experimental Surgery

基　　金：河南省科技厅计划发展项目(LHGJ20210791)。

摘　　要：目的:探讨人内源性反转录病毒-H长末端重复关联蛋白2(HHLA2)在骨肉瘤组织的表达及其临床意义。方法:选取2020年1月至2023年6月郑州市骨科医院手术切除的99例骨肉瘤和癌旁组织作为研究对象,采用蛋白质免疫印迹和荧光定量PCR分析HHLA2蛋白质和mRNA表达水平;免疫组织化学分析Janus激酶2(JAK2)和信号转导子与转录激活子(STAT3)蛋白表达水平。分析HHLA2表达水平与JAK2-STAT3表达的相关性。分析HHLA2与骨肉瘤患者临床病理特征和预后的关系;采用多因素回归分析影响骨肉瘤患者预后的主要因素。组间比较采用独立样本 t检验。 结果:癌旁组织HHLA2 mRNA和蛋白质表达水平(0.84±0.20、0.86±0.21)明显低于骨肉瘤组织表达水平(1.78±0.21、1.63±0.24),差异有统计学意义( t=32.190、24.110, P<0.05)。骨肉瘤组织中JAK2表达阳性率为59.60%(59/99),STAT3表达阳性率为75.76(75/99)。骨肉瘤组织中HHLA2蛋白质表达水平与JAK2和STAT3表达阳性率呈正相关( r=1.298、2.014, P<0.05)。软骨母细胞瘤和成骨母细胞瘤患者骨肉瘤组织中HHLA2蛋白质表达水平(1.60±0.29、1.65±0.21)比较,差异无统计学意义( t=0.938, P>0.05)。Ⅰ~Ⅱ期患者骨肉瘤组织中HHLA2蛋白质表达水平(1.49±0.14)低于Ⅲ期患者(1.85±0.19),差异有统计学意义( t=11.060, P<0.05)。未淋巴结转移患者骨肉瘤组织中HHLA2蛋白质表达水平(1.51±0.19)低于淋巴结转移患者(1.83±0.17),差异有统计学意义( t=8.602, P<0.05)。中高分化患者骨肉瘤组织中HHLA2蛋白质表达水平(1.72±0.21)低于淋巴结转移患者(1.54±0.24),差异有统计学意义( t=4.129, P<0.05)。预后不良组患者41例,占41.41%;预后良好组58例,占58.59%。预后不良组患者骨肉瘤组织中HHLA2蛋白质表达水平(1.76±0.19)低于预后良好组患者(1.54±0.23),差异有统计学意义( t=4.852, P<0.05)。骨肉瘤组织中HHLA2表达曲线下面积为0.890。标准差为0.045,95%可信区间( CI)为0Objective To investigate the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2(HHLA2)in osteosarcoma and its clinical significance.Methods 99 cases of osteosarcoma and adjacent tissues resected in Zhengzhou orthopedic hospital from January 2023 to June 2024 were selected as the research objects.The protein and mRNA expression levels of HHLA2 were analyzed by Western blotting and fluorescence quantitative PCR.The protein expression levels of Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were analyzed by immunohistochemistry.The correlation between HHLA2 expression level and JAK2-STAT3 expression was analyzed.The relationship between HHLA2 and the clinicopathological characteristics and prognosis of osteosarcoma patients was analyzed.Multivariate regression analysis was used to analyze the main factors affecting the prognosis of patients with osteosarcoma.The measurement data between groups were compared by independent sample t test.ResultsThe expression levels of HHLA2 mRNA and protein in adjacent tissues(0.84±0.20,0.86±0.21)were significantly lower than those in osteosarcoma tissues(1.78±0.21,1.63±0.24,t=32.190,24.110,P<0.05).The positive rate of JAK2 expression and STAT3 expression in osteosarcoma tissues was 59.60%(59/99)and 75.76%(75/99).The expression level of HHLA2 protein in osteosarcoma tissues was correlated with the positive rates of JAK2 and STAT3 expression(r=1.298,2.014,P<0.05).There was no significant difference in the expression level of HHLA2 protein in osteosarcoma tissues between chondroblastoma and osteoblastoma patients(1.60±0.29,1.65±0.21,t=0.938,P>0.05).The expression level of HHLA2 protein in osteosarcoma tissues of stageⅠ-Ⅱpatients(1.49±0.14)was significantly lower than that of stageⅢpatients(1.85±0.19,t=11.060,P<0.05).The expression level of HHLA2 protein in osteosarcoma tissues of patients without lymph node metastasis(1.51±0.19)was significantly lower than that of patients with lymph node met

关 键 词：骨肉瘤 内源性反转录病毒-H长末端重复关联蛋白2 临床病理特征 预后 Janus激酶2和信号转导子与转录激活子信号通路 

分 类 号：R738.1[医药卫生—肿瘤]