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Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers

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Tumor Biology

Abstract

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

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Acknowledgments

The work was financially supported by the Indian Council of Medical Research, New Delhi, India. Reference number 5/13/28/2010/NCD-III.

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Author notes

  1. Lakshmi Krishnamoorthy

    Present address: Department of Biochemistry, Sri Shankara Cancer Hospital and Research Centre, Bangalore, 560004, India

Authors and Affiliations

  1. Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, 560029, India

    J. Bhaskari, V. Shilpa, B. Rahul, G. Ramesh & Lakshmi Krishnamoorthy

  2. Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

    C. S. Premalata

  3. Department of Gynec-Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

    V. R. Pallavi

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  1. J. Bhaskari
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Correspondence to Lakshmi Krishnamoorthy.

Electronic supplementary material

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Table S1

Demographic details of cases recruited. (DOC 44 kb)

Table S2

PCR primers and respective annealing temperatures of SNPs (DOC 30 kb)

Table S3

An analysis of the polymorphisms under the dominant and recessive models. (DOC 34 kb)

Figure S1

LD plot depicting linkage between studied polymorphisms (DOC 26 kb)

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Bhaskari, J., Premalata, C.S., Shilpa, V. et al. Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers. Tumor Biol. 37, 1017–1023 (2016). https://doi.org/10.1007/s13277-015-3891-3

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  • DOI: https://doi.org/10.1007/s13277-015-3891-3

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