Department of Gynecology and Obstetrics, School of Medical Sciences, State University of Campinas, UNICAMP, Tessalia Vieira de Camargo Street, 126, Campinas, Sao Paulo, 13083-887, Brazil.
School of Pharmacy, Federal University of Goias, 240 Street, Leste Universitario, Goiania, Goias, 74605-170, Brazil.
BMC Cancer. 2020 Jul 15;20(1):660. doi: 10.1186/s12885-020-07150-3.
Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis.
This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses.
High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03; p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival.
High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis.
基质金属蛋白酶 2、9 和 14（MMP-2、MMP-9、MMP-14）、金属蛋白酶组织抑制剂 1 和 2（TIMP-1、TIMP-2）以及血管内皮生长因子 A（VEGF-A）的表达通过细胞外基质降解和血管生成参与肿瘤侵袭和转移。本研究旨在评估肿瘤和肿瘤周围基质中 MMP-2、MMP-9、MMP-14、TIMP-1 和 TIMP-2 的表达与宫颈癌预后是否相关。
本研究分析了 64 例患者的回顾性队列。通过免疫组织化学法从前瞻性队列的活检标本中获得蛋白表达，该标本同时包含肿瘤和基质。根据 ROC 曲线的截断值，将染色细胞的表达和百分比分为高或低。通过从诊断到最后一次临床就诊收集随访数据。临床状态分为无疾病存活、有疾病存活、因其他原因死亡和死于疾病。使用特定于原因的 Cox 回归模型，使用 95%置信区间（95%CI）评估根据蛋白表达的疾病相关死亡风险比。对于显著相关性（p<0.05），对低表达和高表达患者绘制了竞争风险生存曲线分析的生存曲线。
基质中 MMP-2（RR；95%CI：3.91；1.17-13.02）和 TIMP-2（RR，95%CI：8.67；1.15-65.27）的高表达水平与疾病相关死亡的相对风险增加和生存率降低相关（p=0.03；p=0.04），而低表达水平与生存率降低相关。基质中 MMP-9（RR，95%CI：0.19；0.05-0.65）和肿瘤中 MMP-9（HR，95%CI：0.19；0.04-0.90）的低表达水平是疾病相关死亡的保护因素，与较差的生存率相关。
基质中 MMP-2 和 TIMP-2 的高表达水平与宫颈癌患者的生存不良显著相关。MMP-9 的高表达与宫颈癌的良好预后相关。
