High VEGFR1/2 expression levels are predictors of poor survival in patients with cervical cancer

Dang, Yunzhi; Zhang, Ying; Li, Jianping; Hu, Jing; Li, Weiwei; Li, Pei; Wei, Lichun; Shi, Mei

doi:10.1097/md.0000000000005772

Cited by 22 publications

(22 citation statements)

References 18 publications

(20 reference statements)

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“…38,39 Some research studies showed that high expression of the KDR gene was associated with worse PFS and OS in patients with NSCLC 40 and cervical cancer. 41 These findings are consistent, to some extent, with those of our study. Inevitably, this study was characterized by some limitations.…”

Section: Dovepresssupporting

confidence: 93%

Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism

Song

Zhao

Zuo

et al. 2020

OTT

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Purpose: This study investigated the clinical outcomes and safety of apatinib mesylate in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in patients who progressed after standard therapy, and analyzed the kinase insert domain receptor (KDR) gene polymorphism. Methods: A total of 135 patients with advanced non-squamous NSCLC who received apatinib mesylate were included. Objective response rates were evaluated. Subsequently, progression-free survival (PFS) and overall survival (OS) were assessed and safety data were recorded. Additionally, peripheral blood and biopsy cancer tissue specimens were collected from the patients with NSCLC for the genotyping of the genetic polymorphism and mRNA expression of the KDR gene, respectively. Analysis on the association between genotypes and prognosis was conducted. Results: The objective response rate of the 135 patients with NSCLC was 18.52%, disease control rate was 65.19%, median PFS was 3.95 months, and median OS was 10.05 months. Regarding the KDR gene polymorphism analysis, the distribution of the 4397T>C polymorphism genotypes was in accordance with the Hardy-Weinberg Equilibrium (P=0.868). Moreover, the prognosis analysis indicated that the median PFS of patients with the CC/TC and TT genotypes was 2.80 and 4.80 months, respectively (P=0.002). Furthermore, the median OS of patients with the two genotypes was 9.10 and 10.56 months, respectively (P=0.041). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for PFS (odds ratio: 1.72, P=0.009). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression analysis suggested that the mRNA levels of KDR in cancer tissues were significantly different between the TT and TC/CC genotypes (P<0.001). Conclusion: The clinical outcomes of treatment with apatinib mesylate for advanced nonsquamous NSCLC in patients who progressed after standard therapy may be influenced by the KDR 4397T>C polymorphism through mediation of the mRNA expression of KDR.

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Section: Dovepresssupporting

confidence: 93%

Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism

Song

Zhao

Zuo

et al. 2020

OTT

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“…However, because the upregulation of these receptor genes of vascular endothelial precursor cells that normalised to CD34 gene was not observed in a tumour niche, the upregulation of these receptor genes might occur mainly in tumour cells. Although these genes are mainly expressed in vascular endothelial cells and perivascular cells, they were occasionally observed to be upregulated in several types of tumours (Plate et al 1992;Brown et al 2000;Dang et al 2017). Taken together, these results indicated that the upregulation of angiogenesis-related genes may be important for canine tumourigenesis, and VEGFR-2 may be a candidate target gene for cancer therapy regardless of the benign or malignant status of the tumour.…”

Section: Discussionmentioning

confidence: 80%

“…; Dang et al . ). Taken together, these results indicated that the upregulation of angiogenesis‐related genes may be important for canine tumourigenesis, and VEGFR‐2 may be a candidate target gene for cancer therapy regardless of the benign or malignant status of the tumour.…”

Section: Discussionmentioning

confidence: 97%

“…VEGFRs are expressed not only in vascular endothelial cells, but also in many tumour types, and they mediate VEGF signalling in tumour cells (Goel & Mercurio ; Dang et al . ). Signal transduction of VEGFR‐1 and VEGFR‐2 promotes survival and growth of vascular endothelial cells (Ferrara et al .…”

Section: Introductionmentioning

confidence: 97%

“…VEGF-A signalling is mediated by the receptor tyrosine kinases VEGF receptor-1 (VEGFR-1, also known as Flt-1) and VEGF receptor-2 (VEGFR-2, also known as KDR or Flk-1) (Takahashi et al 2001;Ferrara et al 2003;Goel & Mercurio 2013). VEGFRs are expressed not only in vascular endothelial cells, but also in many tumour types, and they mediate VEGF signalling in tumour cells (Goel & Mercurio 2013;Dang et al 2017). Signal transduction of VEGFR-1 and VEGFR-2 promotes survival and growth of vascular endothelial cells (Ferrara et al 2003;Shibuya & Claesson-Welsh 2006).…”

Section: Introductionmentioning

confidence: 99%

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Angiogenesis‐related gene expression profile in clinical cases of canine cancer

Tanabe

Kobayashi

Maeda

et al. 2018

Veterinary Medicine & Sci

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The balance between pro‐ and anti‐angiogenic signalling is tightly regulated in normal tissues to maintain the functions of the vasculature. In contrast, the overproduction of angiogenic factors and enhanced angiogenesis are frequently observed in several types of tumours. Although there have been many reports on the correlation between tumour progression and angiogenesis in humans, little is known about tumour angiogenesis in canines. Hence, we attempted to clarify whether angiogenesis contributes to tumour progression in canines as well as humans. In this study, we investigated the expression of several angiogenesis‐related genes, including CD 34 , VEGF ‐A , VEGFR ‐1 , VEGFR ‐2 , Ang‐1 , Ang‐2 , Tie1, and Tie2 , in 66 canine tumour tissues and in the normal tissues surrounding the tumours by quantitative real‐time PCR analysis. Our comparative analysis between canine tumour tissues and normal tissues revealed that several angiogenesis‐related genes, such as vascular endothelial growth factor ( VEGF ) and VEGF ‐receptor genes, were significantly upregulated in canine tumour tissues when compared to the normal tissues. We also found that the angiopoietin ( Ang ) ‐1/Ang‐2 gene expression ratio was lower in canine tumour tissues than in the normal tissues, suggesting less association between vascular endothelial cells and perivascular cells in the canine tumour tissues. Taken together, our results suggest that several angiogenesis‐related genes may contribute to the malignant progression of canine tumours via tumour angiogenesis.

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