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PAI-1、CAIX 和 VEGFA 的表达可作为口腔鳞状细胞癌的预后标志物。

PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

机构信息

Programa de Pós-Graduação em Biotecnologia - RENORBIO, Universidade Federal do Espírito Santo, Vitória, ES, Brazil.

Departamento de Medicina Veterinária, Universidade Federal do Espírito Santo, Campus Alegre, Alegre, ES, Brazil.

出版信息

J Oral Pathol Med. 2018 Jul;47(6):566-574. doi: 10.1111/jop.12721. Epub 2018 May 15.

Abstract

BACKGROUND

In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC.

MATERIALS AND METHODS

Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed.

RESULTS

Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035).

CONCLUSION

Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

摘要

背景

在口腔鳞状细胞癌(OSCC)中,HIF-1 复合物促进与缺氧条件下特定细胞存活机制相关基因的表达,如纤溶酶原激活物抑制剂-1(PAI-1)、碳酸酐酶 9(CAIX)和血管内皮生长因子 A(VEGFA)。本研究旨在探讨 PAI-1、CAIX 和 VEGFA 在 OSCC 中的存在及其预后价值。

材料和方法

采用免疫组织化学法分析 52 例接受手术治疗的 OSCC 患者肿瘤组织标本中这些蛋白的表达情况,所有患者均接受至少 24 个月的随访。分析蛋白表达与临床病理参数及预后的相关性。

结果

PAI-1 膜表达阳性与局部疾病复发显著相关(P=0.027)。多变量分析显示,与阴性表达相比,PAI-1 膜表达阳性是局部疾病复发的独立标志物,风险约增加 14 倍(OR=14.49;CI=1.40-150.01,P=0.025)。PAI-1 细胞质强表达与分化程度较低显著相关(P=0.027)。CAIX 膜表达阳性与局部无病生存显著相关(P=0.038)。CAIX 细胞质表达阳性与淋巴结受累显著相关(P=0.025),与疾病特异性生存显著相关(P=0.022)。多变量分析显示,与阴性表达相比,CAIX 细胞质表达阳性是疾病相关死亡的独立危险因素,其风险约增加 3 倍(HR=2.84;CI=1.02-7.87,P=0.045)。VEGFA 细胞质表达阳性与分化程度较低显著相关(P=0.035)。

结论

我们的研究结果提示,这些表达谱可能作为 OSCC 患者的肿瘤预后标志物。

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