Altered Expression of Endogenous Soluble Vascular Endothelial Growth Factor Receptor-2 Is Involved in the Progression of Esophageal Squamous Cell Carcinoma

Abstract

Endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2), a new splicing variant of VEGFR-2, was shown to be the first endogenous specific inhibitor of lymphatic vessel growth. The expression of esVEGFR-2 and its clinicopathological roles in esophageal squamous cell carcinoma (ESCC) are unclear. In this article, quantitative RT-PCR was employed to detect the mRNA levels of esVEGFR-2 and VEGF-C in 90 paired primary ESCC tissues, along with immunohistochemical staining to measure esVEGFR-2 protein in 182 ESCC primary tissues. Correlations between esVEGFR-2 expression and clinicopathological features were also analyzed. Compared with the corresponding non-neoplastic esophageal mucosa tissues, the mRNA level of esVEGFR-2 was decreased, whereas the mRNA level of VEGF-C was increased in ESCCs. Downregulation of esVEGFR-2 mRNA level was significantly correlated with pTNM stages (χ(2) = 7.790, p=0.02). Immunohistochemical staining of esVEGFR-2 was inclined to be reduced in ESCC tissues; lower esVEGFR-2 protein expression was related to better prognosis (χ(2) = 6.366, p=0.012), whereas higher esVEGFR-2 protein accumulation in ESCC tissues was an independent prognostic factor for poor survival of patients (hazard ratio, 1.606; 95% confidence interval, 1.042-2.476; p=0.032). Taken together, altered expression of esVEGFR-2 is correlated with progression of ESCC. esVEGFR-2 might serve as a new independent prognostic marker for ESCC patients.

Alterations of RNA splicing patterns in esophagus squamous cell carcinoma

“…As an important step in post-transcriptional regulation, AS greatly contributes to proteome diversity, as well as cancer progression and development. As a common phenomenon in cancers, it has been reported that an endogenous soluble form of VEGFR-2, a product of alternative splicing, is present in humans and mice [ 33 ]. Our previous research found that endogenous soluble VEGFR-2 is down-regulated in ESCC, but its high expression is an independent prognostic factor for poor survival [ 33 ].…”

“…As a common phenomenon in cancers, it has been reported that an endogenous soluble form of VEGFR-2, a product of alternative splicing, is present in humans and mice [ 33 ]. Our previous research found that endogenous soluble VEGFR-2 is down-regulated in ESCC, but its high expression is an independent prognostic factor for poor survival [ 33 ]. We identified a novel splice variant of LOXL2 (Lysyl oxidase-like 2), named LOXL2Δ72, which lacks 72 nucleotides encoding 24 amino acids [ 34 ].…”

RAC1 inhibition reverses cisplatin resistance in esophageal squamous cell carcinoma and induces downregulation of glycolytic enzymes

“…The cDNAs were generated from reverse transcription using PrimeScript™ RT‐PCR kit (TaKaRa). Reverse transcription and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) were conducted as described previously (Wu et al , ). qRT‐PCR assays were performed on ABI 7500 Real‐Time PCR system with the primers (Table ) using SYBR Premix Ex Taq (TaKaRa) under the manufacturer's instructions.…”

Alterations of RNA splicing patterns in esophagus squamous cell carcinoma

“…It has been reported that a natural endogenous soluble form of VEGFR-2, a product of alternative splicing, is present in humans and mice [30]. Our previous research found that endogenous soluble VEGFR-2 is down-regulated in ESCC, but its high expression is an independent prognostic factor for poor survival [31]. Previous studies have identi ed at least three isoforms of the human RASSF5 gene, of which RASSF5A is silenced in esophageal tumor cell lines [32].…”