Circulating uPA as a potential prognostic biomarker for resectable esophageal squamous cell carcinoma

Abstract

Previous research showed that the 4 genes of matrix metallopeptidase 9 (MMP9), cyto-keratin 20 (CK20), cyto-keratin 19 (CK19) and urokinase type plasminogen activator (uPA) are detectable in the peripheral blood. All the 4 genes are related to tumor invasion and metastasis. However, whether their expression is associated with clinicopathologic factors and the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is still confused. Expression levels of MMP9, CK20, CK19, and uPA were evaluated by quantificational real-time polymerase chain reaction (qRT-PCR) in peripheral blood of 205 ESCC patients who received radical resection. The cut-off value was 1000 copy numbers. Their impacts on clinicopathologic factors and survival were investigated. The uPA expression positively correlated with gender (P = .046) and tumor size (P = .046). Meanwhile, CK19 expression positively correlated with tumor size (P = .029), vascular invasion (P = .024), and CK20 expression positively correlated with tumor size (P = .035) and degrees of differentiation (P = .032). Moreover, the overexpression of MMP9 has a correlation with postoperative radiotherapy (P = .041) and chemotherapy (P = .012). Among the 4 genes, only uPA is a prognostic indicator for disease-free survival and overall survival both in univariate analysis and multivariate analysis (P = .015). This study suggests that circulating uPA mRNA in peripheral blood can serve as a potential unfavorable prognosis biomarker in ESCC. Further perspective, multi-center and large-scale study is still needed.

PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts, promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway

“…We found that overexpression of PLAU in ESCC is associated with poor prognosis, and PLAU potentially serves as a prognostic marker. Consistent with previous studies, high PLAU expression promotes the progression of ESCC 35 , and other various tumors, including breast, bladder, and lung cancer 21,22,27 . We found that PLAU promotes ESCC proliferation and tumor growth by activating the MAPK pathway.…”

Histomorphological Characteristics and Pathological Types of Hyperproliferation of Gastric Surface Epithelial Cells

“…CK20 expression is accepted to be related to tumor invasion and metastasis. Consistently, in the present study, CK20 is found to be positively expressed (+) in the cases of low-grade neoplasia of epithelial cells and highgrade neoplasia of epithelial cells, while negatively expressed in other cases (Table 2) [24]. Prerequisite of tumor growth is the rapid blood vessel formation (angiogenesis) to support nutrients and oxygen for highly proliferating tumor cells [14].…”

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

“…Both MMPs and the uPA systems are serine proteases that mediate tumor progression through degradation of the ECM. High MMP11 expression has been found to be closely associated with poor prognosis in ESCC 31 , and circulating PLAU mRNA in peripheral blood can potentially serve as a biomarker of unfavourable prognosis in ESCC 32 . SERPINE1 has numerous pro-tumorigenic functions in sustaining proliferative signalling, resisting tumour cell death, and promoting angiogenesis, invasion, metastasis and cancer inflammation 33 .…”