Overexpression of VEGF-C and MMP-9 predicts poor prognosis in Kazakh patients with esophageal squamous cell carcinoma

Abstract

Vascular endothelial growth factor (VEGF) and Matrix metalloproteinases (MMPs) are believed to participate in infiltration of tumors. High mortality of esophageal squamous cell carcinoma (ESCC) related to its primary infiltration; however, it is not clear whether the expression of VEGF and MMPs is involved in this process. Screening of The Cancer Genome Atlas (TCGA) database showed that among the VEGF family and MMP9, VEGF-A, VEGF-C, and MMP-9 mRNA were overexpression in ESCC. This result was verified using the Oncomine database and in Kazakh patients with ESCC. Overexpression of VEGF-C and MMP-9 and positive association with advanced esophageal cancer and invading ESCC cells (Gene Expression Omnibus (GEO): GSE21293). Immunohistochemical staining revealed that VEGF-C and MMP-9 were overexpressed in Kazakh ESCCs. VEGF-C expression was related to invasive depth, tumor-node-metastasis (TNM) staging, lymphatic, and lymph node metastasis of ESCC. The linear association between them was further confirmed in TCGA database and the specimens from Kazakh patients with ESCC. Patients with both proteins expression had tumors with greater aggressiveness, suffered from poor prognosis compared with patients who did not express either protein or expressed protein alone. Both proteins expression predicted high invasiveness of ESCC, which is related to worse prognosis of Kazakh ESCCs.