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0.767~0.948( P<0.05)。诊断的灵敏度84.69%,特异性为85.89%,准确度为78.95%。高Eneeking分期、远端转移和高HHLA2水平是骨肉瘤患者死亡的主要危险因素( P<0.05)。 结论:HHLA2在骨肉瘤组织中呈高水平表达,与JAK2-STAT3信号通路密切相关,HHLA2、JAK2和STAT3表达水平可作为骨肉瘤临床恶性病理特征和预后的辅助诊断标志。
Objective 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 metastasis(1.83±0.17,t=8.602,P<0.05).The expression level of HHLA2 protein in osteosarcoma tissues of patients with medium to high differentiation(1.72±0.21)was significantly lower than that in patients with lymph node metastasis(1.54±0.24,t=4.129,P<0.05).There were 41 patients in the poor prognosis group,accounting for 41.41%;58 cases(58.59%)in the good prognosis group.The protein expression level of HHLA2 in osteosarcoma tissues of patients with poor prognosis(1.76±0.19)was significantly lower than that of patients with good prognosis(1.54±0.23,t=4.852,P<0.05).The area under the curve of hhla2 expression in osteosarcoma tissues was 0.890.The standard deviation was 0.045,and the 95%confidence interval(CI)was 0.767-0.948(P<0.05).The sensitivity,specificity and accuracy of diagnosis were 84.69%,85.89%and 78.95%,respectively.High Eneeking stage,distal metastasis and high HHLA2 level were the main risk factors for death in patients with osteosarcoma(P<0.05).Conclusion HHLA2 is highly expressed in osteosarcoma tissues and is closely related to JAK2-STAT3 signaling pathway.The expression levels of HHLA2,JAK2 and STAT3 can be used as auxiliary diagnostic markers for the clinical malignant pathological characteristics and prognosis of osteosarcoma.
作者
窦浚峰
严磊
张景义
王少华
周宇
封青川
海国栋
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)
出处
《中华实验外科杂志》
CAS
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)。
作者简介
通信作者:海国栋,Email:haiwenhappy@126.com。
