胃肠道间质瘤组织中USP47、GLI-1、HIF-1α的表达及意义

Expression and Significance of USP47, GLI-1 and HIF-1α in Gastrointestinal Stromal Tumors

摘要: 目的：探讨泛素特异性蛋白酶47 (ubiquitin-specific protease 47, USP47)、神经胶质瘤相关癌基因同源物1 (glioma-associated oncogene homolog 1, GLI-1)及缺氧诱导因子-1α (hypoxia inducible factor-1α, HIF-1α)在胃肠道间质瘤(gastrointestinal stromal tumor, GIST)组织中的表达及临床意义。方法：采用免疫组化SP法检测103例GIST组织中USP47、GLI-1和HIF-1α的表达。分析其表达与患者临床病理特征及预后的关系，并分析三指标表达间的相关性。结果：USP47、GLI-1和HIF-1α在103例GIST组织中阳性表达率分别为79.6% (82/103)、60.2% (62/103)和58.3% (60/103)。三者的表达与肿瘤大小、肿瘤部位、危险度分级有关(P < 0.05)，与年龄及性别无关。GLI-1和HIF-1α的表达与核分裂象有关(P < 0.05)。生存分析显示，USP47、GLI-1和HIF-1α高表达组患者总生存率均显著低于低表达组(P < 0.05)。Spearman相关性分析显示，USP47与GLI-1 (r = 0.407, P < 0. 001)、USP47与HIF-1α (r = 0.253, P < 0.05)及GLI-1与HIF-1α (r = 0.338, P < 0. 001)表达呈正相关。结论：USP47、GLI-1和HIF-1α在GIST中高表达，且三者表达呈正相关，其表达水平均与GIST的恶性进展及患者总生存期显著相关。联合检测三者表达有助于GIST患者的危险度分层和预后判断，为精准治疗提供了新的潜在靶点和理论依据。

Abstract: Objective: To investigate the expression and clinical significance of ubiquitin-specific protease 47 (USP47), glioma-associated oncogene homolog 1 (GLI-1), and hypoxia-inducible factor-1α (HIF-1α) in gastrointestinal stromal tumor (GIST) tissues. Methods: The expressions of USP47, GLI-1, and HIF-1α were detected in 103 GIST tissue samples using streptavidin-peroxidase (SP) immunohistochemistry. Their relationships with clinicopathological characteristics and patient prognosis were analyzed, and the correlations among the expression levels of these three markers were assessed. Results: The positive expression rates of USP47, GLI-1, and HIF-1α in the 103 GIST tissues were 79.6% (82/103), 60.2% (62/103), and 58.3% (60/103), respectively. The expression of all three proteins was associated with tumor size, tumor location, and risk classification (P < 0.05), but not with age or gender. The expression of GLI-1 and HIF-1α was also associated with mitotic count (P < 0.05). Survival analysis revealed that the overall survival rates of patients in the high-expression groups of USP47, GLI-1, and HIF-1α were significantly lower than those in the low-expression groups (P < 0.05). Spearman correlation analysis showed positive correlations between USP47 and GLI-1 (r = 0.407, P < 0.001), USP47 and HIF-1α (r = 0.253, P < 0.05), and GLI-1 and HIF-1α (r = 0.338, P < 0.001). Conclusion: USP47, GLI-1, and HIF-1α are highly expressed in GIST, and their expression levels are positively correlated with each other. The expression levels of all three proteins are significantly associated with malignant progression of GIST and patient overall survival. Combined detection of their expressions may aid in risk stratification and prognosis assessment of GIST patients, providing potential new targets and a theoretical basis for precise treatment.