高温需求因子A1在甲状腺髓样癌组织中的表达及其临床意义  

Expression of high-temperature requirement factor A1 in medullary thyroid carcinoma tissues and its clinical significance

作　　者：眭怡群[1] 夏维[1] SUI Yiqun;XIA Wei(Department of Pathology,the Second Affiliated Hospital of Soochow University,Jiangsu Suzhou 215000,China)

机构地区：[1]苏州大学附属第二医院病理科,江苏苏州215000

出　　处：《现代肿瘤医学》2025年第1期38-44,共7页Journal of Modern Oncology

摘　　要：目的:评估高温需求因子A1(high-temperature requirement factor A1,HTRA1)在甲状腺髓样癌(medullary thyroid carcinoma,MTC)组织中的表达,并探讨其与临床病理特征、预后及肿瘤免疫的关系。方法:采用免疫组化法检测26例MTC组织中HTRA1蛋白的表达。分析HTRA1蛋白表达与临床病理特征及预后的相关性。通过生物信息学揭示HTRA1表达与肿瘤免疫的相关性。结果:HTRA1蛋白在MTC组织中主要定位于细胞浆,而在正常甲状腺组织中主要定位于细胞核。与正常甲状腺组织相比,MTC组织中HTRA1蛋白表达上调。临床病理分析显示,HTRA1蛋白表达与甲状腺被膜外侵犯、桥本氏甲状腺炎及患者的无复发生存期有关。HTRA1蛋白、术前血清降钙素及癌胚抗原的联合检测对甲状腺被膜外侵犯、肿瘤大小、肿瘤T分期及患者无复发生存期的预测价值较高。免疫浸润分析显示,HTRA1表达主要与免疫抑制细胞有关。肿瘤免疫功能障碍和排斥(tumor immune dysfunction and exclusion,TIDE)算法揭示,MTC中HTRA1表达与TIDE评分、免疫功能障碍评分、免疫排斥评分和癌相关成纤维细胞水平呈正相关;与微卫星不稳定性呈负相关。基因集富集分析结果显示,MTC中HTRA1表达主要与细胞外基质及其相关信号通路有关。结论:HTRA1可能成为MTC新的治疗靶点。HTRA1与肿瘤免疫功能的关联可能有助于MTC的免疫治疗。Objective:To evaluate the expression of high-temperature requirement factor A1(HTRA1)in medullary thyroid carcinoma(MTC)tissues and to explore its relationship with clinicopathological features,prognosis and tumor immunity.Methods:The expression of HTRA1 protein in 26 cases of MTC tissue was detected by immunohistochemistry.The correlations between HTRA1 protein expression and clinicopathological features and prognosis were analyzed.The relationship between HTRA1 expression and tumor immunity was revealed through bioinformatics.Results:HTRA1 proteins were mainly localized in the cytoplasm in MTC tissues,whereas they were mainly localized in the nucleus in normal thyroid tissues.HTRA1 protein expression was up-regulated in MTC tissues compared with normal thyroid tissues.Clinicopathological analysis showed that the expression of HTRA1 protein was associated with extrathyroidal extension,Hashimoto's thyroiditis and recurrence-free survival.The combined detection of HTRA1 protein,preoperative serum calcitonin and carcinoembryonic antigen had a higher value in predicting extrathyroidal extension,tumor size,tumor T stage and recurrence-free survival.Immunoinfiltration analysis showed that HTRA1 expression was mainly related to immunosuppressive cells.The tumor immune dysfunction and exclusion(TIDE)algorithm revealed that HTRA1 expression in MTC was positively correlated with TIDE score,immune dysfunction,immune exclusion and cancer-associated fibroblast,while it was negatively correlated with microsatellite instability.Gene set enrichment analysis showed that in MTC,HTRA1 expression was mainly associated with gene sets of extracellular matrix and its related signaling pathways.Conclusion:HTRA1 may serve as a new therapeutic target for MTC.The association of HTRA1 with tumor immune function may be helpful for immunotherapy of MTC.

关 键 词：HTRA1 甲状腺髓样癌 肿瘤免疫 细胞外基质 

分 类 号：R736.1[医药卫生—肿瘤]