肾上腺皮质癌组织中COX-2蛋白表达与临床病理特征及预后的关系研究

Relationship of expression of COX-2 with clinicopathological parameters and prognosis in adrenal sebaceous carcinoma tissues

摘要:

目的 探讨肾上腺皮质癌（ACC）组织中环氧合酶-2（COX-2）蛋白表达与临床病理特征及预后的关系。方法 从癌症基因组图谱（TCGA）数据库中获得51例经手术病理确诊为ACC的患者，术后随访3年。比较癌组织、癌旁组织中COX-2蛋白阳性表达率；分析不同临床病理特征ACC患者癌组织中COX-2蛋白阳性表达率的差异；多因素Cox比例风险模型分析影响ACC患者预后的因素；分析癌组织中COX-2阳性表达与ACC患者生存的关系。结果 ACC患者癌组织中COX-2阳性表达率高于癌旁组织中COX-2阳性表达率（P <0.05）。低分化、Ⅲ期、CD56阳性、Syn阳性、Ki-67表达≥ 10%、微血管侵犯的ACC患者癌组织中COX-2阳性表达率分别高于中高分化、Ⅰ和Ⅱ期、CD56阴性、Syn阴性、Ki-67表达< 10%、未合并微血管侵犯的ACC患者癌组织中COX-2阳性表达率（P <0.05）。多因素Cox比例风险模型分析结果显示，病理分级［R^R=4.904（95% CI：2.018，11.918）、分期［R^R=6.025（95% CI：2.479，14.644）］、内分泌功能［R^R=3.927（95% CI：1.616，9.545）］、Ki-67［R^R=4.011（95% CI：1.650，9.748）］、COX-2阳性［R^R=5.114（95% CI：2.104，12.429）］是影响ACC患者术后复发的危险因素（P <0.05）；病理分级［R^R=4.914（95% CI：2.022，11.942）］、分期［R^R=6.633（95% CI：2.729，16.119）］、内分泌功能［R^R=4.003（95% CI：1.647，9.728）］、COX-2阳性［R^R=5.296（95% CI：2.179，12.872）］是影响ACC患者术后生存的危险因素（P <0.05）。COX-2阳性表达患者与COX-2阴性表达患者的无病生存曲线及总存活曲线比较，差异有统计学意义（P <0.05）。结论 ACC患者癌组织中COX-2蛋白阳性表达与临床病理特征及预后有关，COX-2阳性患者预后不良风险高。

Abstract:

Objective To investigate the relationship of the expression of cyclooxygenase-2 (COX-2) with clinicopathological parameters and early recurrence after resection in adrenal sebaceous carcinoma (ACC) tissues.Methods Fifty one patients assessed with COX-2 gene expression with ACC in The Cancer Genome Atlas (TCGA) and were followed up for 3 years postoperatively. Immunohistochemistry was used to detect COX-2 protein expression; COX-2 protein expression in cancer tissues and paracancerous tissues were compared; The relationship between COX-2 expression in cancer tissues and clinicopathological parameters, factors affecting the prognosis, and the relationship between COX-2 expression in cancer tissues and survival of ACC patients were analyzed.Results The positive expression rate of COX-2 in cancer tissues of ACC patients was higher than that of paraneoplastic tissues (P < 0.05). The COX-2 positive expression rates in cancer tissues of ACC patients with low differentiation, stage Ⅲ, CD56 positive, Syn positive, Ki-67 expression ≥ 10%, and microvascular invasion were higher than those with moderate to high differentiation, stage Ⅰ to Ⅱ, CD56 negative, Syn negative, Ki-67 expression < 10%, and no combined microvascular invasion, respectively (P < 0.05). Cox regression analysis showed that pathological grade [R^R = 4.904 (95% CI: 2.018, 11.918) ], stage [R^R = 6.025 (95% CI: 2.479, 14.644) ], endocrine function [R^R= 3.927 (95% CI: 1.616, 9.545) ], Ki-67 expression [R^R = 4.011 (95% CI: 1.650, 9.748) ] and COX-2 positive [R^R = 5.114 (95% CI: 2.104, 12.429) ] were risk factors affecting postoperative recurrence in ACC patients (P < 0.05). Cox regression analysis showed that pathological grade [R^R =4.914 (95% CI: 2.022, 11.942) ], stage [R^R = 6.633 (95% CI: 2.729, 16.119) ], endocrine function [R^R = 4.003 (95% CI: 1.647, 9.728) ], and COX-2 positive [R^R = 5.296, (95% CI: 2.179, 12.872) ] were risk factors affecting the postoperative survival of ACC patients (P < 0.05). The differences in disease-free survival curves and overall survival curves between patients with positive COX-2 expression and patients with negative COX-2 expression were statistically significant (P < 0.05).Conclusion COX-2 protein expression in cancer tissues of ACC patients is related to clinicopathological parameters and prognosis, and COX-2-positive patients have a high risk of poor prognosis.