DOI: https://doi.org/10.14710/jbtr.v7i3.11681

Diagnostic Value of Vascular Endothelial Growth Factor C (VEGF-C) and CA 15-3 in Breast Cancer

Faculty of Medicine, Universitas Diponegoro, Indonesia

Received: 7 Jul 2021; Revised: 6 Dec 2021; Accepted: 17 Dec 2021; Available online: 31 Dec 2021; Published: 31 Dec 2021.
Open Access Copyright (c) 2021 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:
Abstract

ABSTRACT

Background: expression of VEGF-C and CA 15-3 may be useful to differentiate between malignant and benign breast tumour because VEGF-C plays a role in promoting angiogenesis and lymphangiogenesis in malignant processes and CA 15-3 is the soluble form of transmembrane protein MUC1, a tumour marker which shows higher expression in breast cancer.

Objective: to determine the diagnostic value of VEGF-C and CA 15-3 as tumour markers in patients with breast cancer.

Methods: this diagnostic study recruited 76 patients that underwent surgical biopsy procedures at Dr. Kariadi and Pantiwilasa Citarum Hospitals Semarang. The VEGF-C and CA 15-3 levels in blood specimens taken before surgical biopsy procedure was determined using ELISA method. An ROC curve and AUC were used to establish the cut-off points and diagnostic value. Pathology examination results from the biopsy specimens were used as the gold standard.

Results: the cut-off value for VEGF-C and CA 15-3 were 989.50 pg/mL and 74.00 U/mL. Sensitivity for VEGF-C, CA 15-3 and VEGF-C+CA 15-3 were 76.6%, 64.1% and 89.1%. Specificity for VEGF-C, CA 15-3 and VEGF-C+CA 15-3 were 75.0%, 75.0% and 50.0%. The AUC for VEGF-C, CA 15-3 and VEGF-C+CA 15-3 was 0.831 (95% CI = 0.727-0.934), 0.742 (95% CI = 0.628-0.856) and 0.840 (95% CI = 0.742-0.938).

Conclusion: VEGF-C in combination with CA 15-3 is the best diagnostic parameter for breast cancer and has the best accuracy as a tumour marker for breast cancer.

Note: This article has supplementary file(s).

Fulltext View|Download |  common.other
Ethical clearance
Subject Breast cancer, VEGF-C, CA 15-3, tumour marker, diagnostic value.
Type Other
  View (1MB)    Indexing metadata
Keywords: Breast cancer; VEGF-C; CA 15-3; Tumour Marker; Diagnostic Value.

Article Metrics:

Article Info
Section: Original Research Articles
Language : EN
Recent articles
The Effectivity of Thymus vulgaris Extract on IL-1 Level and Bacterial Count in The Heart of Balb-c Mice Infected with MRSA Therapeutic Effect of Red Spinach (Amaranthus tricolor L.) Extract on Pancreatic MDA Levels Rats (Rattus norvegicus) Exposed to MLD-STZ The Differences of Lipoprotein-Associated Phospholipase A2, Apolipoprotein B and Low Density Lipoprotein In Obese and Lean Men Subacute Spinal Subdural Hematoma in One-Year Old Boy Due to Severe Hemophilia A Melatonin, A Promising Therapeutic for Diabetes Mellitus and Its Complications: A Narrative Review More recent articles
  1. Duffy MJ, Evoy D, McDermott EW. CA 15-3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta. 2010;411(23-24):1869-74
  2. Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press). 2019;11:151-4
  3. Zhang Z, Luo G, Tang H, Cheng C, Wang P. Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis. PLoS One. 2016;11(11):e0165725
  4. Sun YS, Zhao Z, Yang ZN, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci. 2017;13(11):1387-97
  5. DeSantis CE, Fedewa SA, Goding Sauer A, et al. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women. CA Cancer J Clin. 2016; 66: 31-42
  6. Trecate G, Sinues PM, Orlandi R. Noninvasive strategies for breast cancer early detection. Future Oncol. 2016;12(11):1395‐411
  7. Zajkowska M, Lubowicka E, Fiedorowicz W, Szmitkowski M, Jamiołkowski J, Ławicki S. Human Plasma Levels of VEGF-A, VEGF-C, VEGF-D, their Soluble Receptor - VEGFR-2 and Applicability of these Parameters as Tumour Markers in the Diagnostics of Breast Cancer. Pathol Oncol Res. 2019;25(4):1477-86
  8. Ouyang Y, Tsui PH, Wu S, Wu W, Zhou Z. Classification of Benign and Malignant Breast Tumours Using H-Scan Ultrasound Imaging. Diagnostics (Basel). 2019;9(4):182
  9. Nigam M, Nigam B. Triple Assessment of Breast – Gold Standard in Mass Screening for Breast Cancer Diagnosis. IOSR-JDMS. 2013;7(3):1-7
  10. Zajkowska M, Głażewska EK, Będkowska GE, Chorąży P, Szmitkowski M, Ławicki S. Diagnostic Power of Vascular Endothelial Growth Factor and Macrophage Colony-Stimulating Factor in Breast Cancer Patients Based on ROC Analysis. Mediators Inflamm. 2016;2016:5962946
  11. Hashim ZM. The significance of CA15-3 in breast cancer patients and its relationship to HER-2 receptor status. Int J Immunopathol Pharmacol. 2014;27(1):45-51
  12. Sunwoo HH, Suresh MR. Cancer Markers. The Immunoassay Handbook (Fourth Edition) Theory and Applications of Ligand Binding, ELISA and Related Techniques. 2013, Pages 833-56
  13. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumour markers in breast cancer. J Clin Oncol. 2007;25(33):5287-312
  14. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumour lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7(2):192-8
  15. van Stralen KJ, Stel VS, Reitsma JB, Dekker FW, Zoccali C, Jager KJ. Diagnostic methods I: sensitivity, specificity, and other measures of accuracy. Kidney Int. 2009 Jun;75(12):1257-1263
  16. Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press). 2019 Apr 10;11:151-164
  17. Kim Y, Yoo K-Y, Goodman MT. Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors. Asian Pac J Cancer Prev. 2015;16(7):2857–70
  18. Assi HA, Khoury KE, Dbouk H, Khalil LE, Mouhieddine TH, El Saghir NS. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis. 2013;5(Suppl 1):S2–S8
  19. Valtola R, Salven P, Heikkilä P, et al. VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol. 1999;154(5):1381-90
  20. Thammineni KL, Thakur GK, Kaur N, Banerjee BD. Significance of MMP-9 and VEGF-C expression in North Indian women with breast cancer diagnosis. Mol Cell Biochem. 2019;457(1-2):93‐103
  21. Fu S, Yun ZY, Cui MM, et al. Cancer antigen 15-3, platelet distribution width, and fibrinogen in combination to distinguish breast cancer from benign breast disease in non-conclusive mammography patients. Oncotarget. 2017;8(40):67829-36
  22. Duffy MJ, Shering S, Sherry F, McDermott E, O'Higgins N. CA 15-3: a prognostic marker in breast cancer. Int J Biol Markers. 2000;15(4):330‐33
  23. Duffy MJ, Walsh S, McDermott EW, Crown J. Biomarkers in Breast Cancer: Where Are We and Where Are We Going? Adv Clin Chem. 2015;71:1‐23
  24. Park S, Ahn HK, Park LC, Hwang DW, Ji JH, Maeng CH, et al. Implications of different CA 15-3 levels according to breast cancer subtype at initial diagnosis of recurrent or metastatic breast cancer. Oncology. 2012;82(3):180-7
  25. Fu Y, Li H. Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis. Med Sci Monit. 2016;22:3154-62
  26. Ławicki S, Będkowska GE, Szmitkowski M. VEGF, M-CSF and CA 15-3 as a new tumour marker panel in breast malignancies: a multivariate analysis with ROC curve. Growth Factors. 2013;31(3):98‐105
  27. Unal I. Defining an Optimal Cut-Point Value in ROC Analysis: An Alternative Approach. Comput Math Methods Med. 2017;2017:3762651
  28. Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010 Sep;5(9):1315-6
  29. Power M, Fell G, Wright M. Principles for high-quality, high-value testing. EvidBased Med. 2013 Feb;18(1):5-10
  30. Yavuz S, Paydas S, Disel U, Zorludemir S, Erdogan S. VEGF-C expression in breast cancer: clinical importance. Adv Ther. 2005 Jul-Aug;22(4):368-80
  31. Begum M, Karim S, Malik A, Khurshid R, Asif M, Salim A, Nagra SA, Zaheer A, Iqbal Z, Abuzenadah AM, Alqahtani MH, Rasool M. CA 15-3 (Mucin-1) and physiological characteristics of breast cancer from Lahore, Pakistan. Asian Pac J Cancer Prev. 2012;13(10):5257-61
  32. Choi JW, Moon BI, Lee JW, Kim HJ, Jin Y, Kim HJ. Use of CA15‑3 for screening breast cancer: An antibody‑lectin sandwich assay for detecting glycosylation of CA15‑3 in sera. Oncol Rep. 2018;40(1):145-54
  33. Storr SJ, Royle L, Chapman CJ, Hamid UMA, Robertson JF, Murray A, Dwek RA and Rudd PM: The O‑linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum. Glycobiology.2008; 18: 456-62
  34. Lavrsen K, Madsen CB, Rasch MG, Woetmann A, Odum N, Mandel U, Clausen H, Pedersen AE and Wandall HH: Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody‑dependent cell‑mediated cytotoxicity. Glycoconj J.2013; 30: 227-36
  35. Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011;31(5):1757-64
  36. Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011 May;31(5):1757-64
  37. Moro F, Pasciuto T, Djokovic D, Di Legge A, Granato V, Moruzzi MC, Mancari R, Zannoni GF, Fischerova D, Franchi D, Scambia G, Testa AC. Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses. Ultrasound Obstet Gynecol. 2019 Jan;53(1):116-123

Last update:

No citation recorded.

Last update:

No citation recorded.