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.
J Oral Pathol Med. 2018 Jul;47(6):566-574. doi: 10.1111/jop.12721. Epub 2018 May 15.
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.
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.
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).
Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.
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。
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。
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）。
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。
