Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Abstract

Abstract. Angiogenesis is important in cancer progression. Promising results in clinical trials have indicated that targeting vascular epidermal growth factor (VEGF) signaling may prolong lung cancer patient survival. In particular, various studies have implicated VEGFA as a potential prognostic marker in lung cancer, although prognostication using the expression of VEGF receptors (VEGFRs), such as fms-related tyrosine kinase 1 (FLT1; also known as VEGFR1) and kinase insert domain receptor (KDR; also known as VEGFR2), has produced varied results in different lung cancer studies. The present study aimed to investigate the prognostic significance of these three factors, alone or in combination. mRNA expression data were extracted from four independent lung cancer cohorts totaling 583 patients, and the association between mRNA expression and survival was investigated by performing statistical analyses. When VEGFA, FLT1 and KDR expression were considered alone, only VEGFA demonstrated a significant association with patient survival consistently across all four datasets (P<0.05). Patients with a high expression of VEGFA and one of the two receptors were associated with significantly worse survival than patients expressing low levels of VEGFA and the particular receptor (P<0.05). Notably, patients with a high level expression of all three genes in their tumor specimens were associated with a significantly shorter survival time compared with patients exhibiting a low level expression of one, two or all three genes (P<0.05). The results indicate that a high level of VEGFA expression and its receptors may be required for cancer progression. Therefore, these three factors should be considered together as a prognostic indicator for lung cancer patients.

The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

“…Our previous report showed that combining VEGFA , FLT1 , and KDR expression could be a better prognostic indicator in lung cancer compared to when these factors were considered individually. 29 In the present study, we have shown that using similar methodology, this three-gene signature is a robust prognostic indicator in colon cancer. Most importantly, this three-gene signature has been shown to predict the response to bevacizumab, an anti-angiogenic agent.…”

“… 7 Antiangiogenic therapy is also a successful strategy in the treatment of lung cancer patients; 27 , 28 we recently reported that a VEGFA-FLT1-KDR gene signature had strong prognostic significance in lung cancer patients. 29 In the present study, we investigated the prognostic significance of the combined mRNA expressions of VEGFA , FLT1 , and KDR in colorectal cancer using colon cancer datasets available in the Gene Expression Omnibus (GEO) database.…”

Lymphatics-associated genes are downregulated at transcription level in non-small cell lung cancer

“…The prognostic value of this receptor expression in NSCLC remains controversial. In several recent studies, an unfavorable effect of high VEGFR1 expression on NSCLC patient' survival has been demonstrated (87,49), whereas others found no correlation between the expression and the prognosis of the disease (88). To resolve discrepancies in the results further investigations are needed.…”

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

“…VEGFA in tumors has also been studied in breast cancer, 67 , 68 laryngeal carcinoma, 69 colorectal cancer, 70 , 71 bladder cancer, 72 and lung cancer. 73 In PC, Liu et al 74 found that VEGFA was involved in the Twist/miR-497/VEGFA axis, which is significantly correlated to metastasis and angiogenesis in PC. VEGFA secretion has also been reported to be regulated by myoferlin and affects tumor-associated angiogenesis in PC.…”