Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India.
Department of Surgery, University College of Medical Sciences & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India.
Mol Cell Biochem. 2019 Jul;457(1-2):93-103. doi: 10.1007/s11010-019-03515-w. Epub 2019 Apr 16.
Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer & benign breast disease (N = 100) were investigated for the mRNA expression of MMP-9 and VEGF-C by Real-time PCR and Protein expression by Western blot. Elevated levels of MMP-9 (p < 0.001) and VEGF-C (p < 0.001) expression were detected in breast cancer with corresponding to benign breast disease. Additionally, we found significantly increased levels of MMP-9 and VEGF-C in node-positive group with respect to node-negative group. Moreover, the levels of MMP-9 were significantly increased in larger tumor size (T3/T4) (p < 0.05) as compared to smaller size (T1/T2), which suggests that MMP-9 plays an important role in the progression of breast cancer. VEGF-C expression was associated with the TNM stage of tumor (p < 0.05). Further, a significant positive correlation was established between the mRNA levels of these two genes (p < 0.001). However, we could not obtain any significant correlation between expression of these genes with other clinicopathological parameters like tumor grade, age, menopausal status, and receptor status like ER, PR, and Her2. This study suggests that the high expression of MMP-9 and VEGF-C could act as markers for the tumor presence in breast cancer. In addition, this study recommends that expression of MMP-9 and VEGF-C was significantly associated with lymph node status and may provide valuable diagnosis of lymph node metastasis in breast cancer patients. Further, MMP-9 expression was associated with the tumor size and VEGF-C expression was correlated with the staging of the tumor, although no association was observed with other clinicopathological variables.
转移是癌症相关死亡的主要原因，使乳腺癌患者的靶向治疗无效。基质金属蛋白酶-9（MMP-9）和血管内皮生长因子-C（VEGF-C）被认为参与肿瘤的进展和转移。本研究旨在探讨 MMP-9 和 VEGF-C 在乳腺癌中的 mRNA 和蛋白水平的表达，并与淋巴结转移和其他临床病理特征相关。通过实时 PCR 检测 100 例乳腺癌和 100 例良性乳腺疾病活检标本中 MMP-9 和 VEGF-C 的 mRNA 表达，通过 Western blot 检测蛋白表达。与良性乳腺疾病相比，乳腺癌中 MMP-9（p<0.001）和 VEGF-C（p<0.001）的表达水平升高。此外，我们发现 MMP-9 和 VEGF-C 在淋巴结阳性组的水平显著高于淋巴结阴性组。此外，与较小的肿瘤大小（T1/T2）相比，较大的肿瘤大小（T3/T4）中 MMP-9 的水平显著增加（p<0.05），这表明 MMP-9 在乳腺癌的进展中起重要作用。VEGF-C 的表达与肿瘤的 TNM 分期有关（p<0.05）。此外，这两个基因的 mRNA 水平之间存在显著的正相关（p<0.001）。然而，我们没有发现这些基因的表达与肿瘤分级、年龄、绝经状态和受体状态（如 ER、PR 和 Her2）等其他临床病理参数之间存在任何显著相关性。本研究表明，MMP-9 和 VEGF-C 的高表达可能作为乳腺癌中肿瘤存在的标志物。此外，本研究表明 MMP-9 和 VEGF-C 的表达与淋巴结状态显著相关，可能为乳腺癌患者的淋巴结转移提供有价值的诊断。此外，MMP-9 的表达与肿瘤大小相关，VEGF-C 的表达与肿瘤分期相关，尽管与其他临床病理变量无相关性。
