骨肉瘤组织中MICA、MMP-9和NF-κB蛋白的表达及相关性

Expression of MICA,MMP-9 and NF-κB and their correlation in osteosarcoma

目的探讨骨肉瘤组织中MHCⅠ类链相关蛋白A(MHC class Ⅰ chain-related A,MICA)、MMP-9和NF-κB的表达及相互间的关系,为研究骨肉瘤组织中MICA蛋白表达和脱落机制提供组织学依据。方法应用免疫组织化学方法检测66例骨肉瘤、11例骨母细胞瘤,8例骨化性纤维瘤和6例正常骨组织中MICA蛋白的表达情况,并检测66例骨肉瘤组织中MMP-9和NF-κB蛋白的表达情况。结果(1)MICA蛋白在骨肉瘤组织、骨母细胞瘤、骨化性纤维瘤和正常骨组织的表达率分别为51.6%(34/66)、9%(1/11)、0(0/8)、0(0/6),骨肉瘤组织中MICA表达与骨母细胞瘤(P=0.01)、骨化性纤维瘤(P<0.01)和正常骨组织(P<0.05的差异有显著性。(2)骨肉瘤组织中MMP-9和NF-κB表达率分别为55%(36/66)和73%(48/66);NF-κB与MICA(r=0.373,P<0.01)和MMP-9(r=0.536,P<0.01)的表达呈正相关关系。结论MICA蛋白可作为骨肉瘤诊断的分子标志物;NF-κB可能参与MICA蛋白表达和脱落的分子机制,NF-κB可作为骨肉瘤免疫治疗的候选靶点。

Purpose To investigate the mechanism of the expression and shedding of MHC class [ chain - related A （ MICA）, and the relationship between MICA, MMP-9 and NF-κB expression in osteosarcoma. Methods MICA expression was examined in 66 cases of osteosareoma, 11 osteoblastoma, 8 ossifying fibroma and 6 normal bone tissues by immunohistochemistry, in which the expression of MMP-9 and NF-κB were also evaluated in the osteosarcoma cases. Results （ 1 ） The expression rates of MICA protein in osteosarcoma, osteoblastoma, ossifying fibrnma and normal bone tissues were 51.6% （34/66）, 9% （ 1/11 ）, 0 （0/8） and 0 （0/6）, respectively. Up-regulation of MICA expression was found in osteosarcoma, compared with osteoblastoma （P = 0. 01 ）, ossifying fibroma （P 〈 0. 01 ） and normal bone tissues （P〈0. 05）. （2） MMP-9 and NF-κB were detected in 55% （36/66） and 73% （48/66） of osteosarcoma, respectively. NF-κB expression increased with elevated expression of MICA （ r = O. 373, P 〈 0. 01 ） and MMP-9 （ r = 0. 536, P 〈 0. 01 ）. Conclusions MICA protein is a useful molecular marker for the diagnosis of osteosarcoma; NF-κB may play a role in the molecular mechanism of the expression and shedding of MICA protein in the osteosarcoma, and it may be a putative target for immunotherapy in osteosarcoma.