Detection of Vascular Endothelial Growth Factor Messenger RNA (VEGF mRNA), Cytokeratin-19 mRNA (CK19 mRNA), and Vascular Endothelial Growth Factor (VEGF) Protein Biomarker in the Peripheral Blood of Patients with Breast Cancer

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Molecular and Cellular Sciences, School of Advance Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

2 Assistant Professor, Virology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital AND Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Assistant Professor, Department of Molecular and Cellular Sciences, School of Advance Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

4 Assistant Professor, Craniomaxillofacial Research center AND Iranian Tissue Bank Research Center AND Department of Oral and Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Breast cancer is a multifactorial potentially lethal disease that is triggered by genetic factors as well as numerous environmental factors. The present research aimed to examine the expression of Vascular endothelial growth factor messenger RNA (VEGF mRNA), cytokeratin-19 mRNA (CK19 mRNA), and vascular endothelial growth factor (VEGF) protein biomarker in the peripheral blood of patients with breast cancer.Methods: 40 patients with breast cancer were compared to 40 healthy individuals. The real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) method was used to determine the expressions of the CK19 mRNA and VEGF mRNA biomarkers in the peripheral blood samples of the healthy participants and the patients. The VEGF protein was also compared using the (ELISA) method.Findings: The positive VEGF mRNA biomarker was observed in 30 of the 40 patients with breast cancer; thus the sensitivity of this marker was 75%. In the healthy participants group, 6 of the 40 participants showed a positive VEGF mRNA biomarker expression. The CK19 mRNA marker was positive in 25 of the 40 patients, which indicated a sensitivity of 62.5%. In the healthy participants group, the positive expression of the CK19 mRNA biomarker was observed in 7 of the 40 participants. VEGF was positive in 27 of the 40 patients. In the control group, 5 of the 40 participants showed the positive expression of this biomarker.Conclusion: In sum, based on the results of this research, the assessed breast cancer tumor markers can be used as screening tests for the early diagnosis of patients. To further prove the findings of this study, more extensive studies with larger sample sizes are recommended.

Keywords

References

  1. Kagami S, Saeki H, Idezuki T, Yano S, Kawabata Y, Okochi H, et al. Epithelioid sarcoma associated with lung adenocarcinoma. J Dermatol 2005; 32(11): 904-8.
  2. American Cancer Society. A Cancer Source Book for Nurses. 8th ed. Sudbury, MA: Jones and Bartlett Learning; 2004.
  3. Pike MC, Henderson BE, Casagrande JT, Rosario I, Gray GE. Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer 1981; 43(1): 72-6.
  4. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283(4): 485-91.
  5. Wynder EL, Rose DP, Cohen LA. Diet and breast cancer in causation and therapy. Cancer 1986; 58(8 Suppl): 1804-13.
  6. Stevens RG. Electric power use and breast cancer: a hypothesis. Am J Epidemiol 1987; 125(4): 556-61.
  7. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 2000; 321(7261): 624-8.
  8. Stratton MR, Ford D, Neuhasen S, Seal S, Wooster R, Friedman LS, et al. Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nat Genet 1994; 7(1): 103-7.
  9. Benlloch S, Galbis J, Peiro F, Alenda C, Rodriguez-Paniagua J, Sanchez-Paya J, et al. Role of CEA, PLUNC and CK19 mRNA expression in lymph nodes from resected stage I non-small cell lung cancer (NSCLC) patients (p) as markers of occult micrometastasis. A pilot study. J Clin Oncol 2005; 23(16Suppl): 9654.
  10. Thomas C, Gustafsson JA. The different roles of ER subtypes in cancer biology and therapy. Nat Rev Cancer 2011; 11(8): 597-608.
  11. Karimi S, Mohamadnia A, Nadji SA, Yadegarazari R, Khosravi A, Bahrami N, et al. Expression of two basic mRNA biomarkers in peripheral blood of patients with non-small cell lung cancer detected by real-time rt-PCR, individually and simultaneously. Iran Biomed J 2015; 19(1): 17-22.
  12. Jamaati H, Bahrami N, Abniki M, Tabarsi P, Farzanegan B, Doroudinia A, et al. Real-time RT-PCR detection of HCN4 and ADAM8 genes in ventilator-associated pneumonia patients Hospitalized in intensive care unit. Journal of Cellular and Molecular Anesthesia 2016; 1(4): 163-7.
  13. Tollefsbol T. Handbook of epigenetics: The new molecular and medical genetics. San Diego, CA: Academic Press; 2010.
  14. Mohamadnia A, Karimi S, Yadegar Azari R, Naji S A, Khosravi A, Bahrami N et al . Expression of CK19 gene in patients with lung cancer and its comparison with carcinoembryonic antigen in peripheral blood. Payavard Salamat 2016; 9(5): 459-68. [In Persian].
  15. Moshref Behzad N, Bahrami N, Farzanegan B, Fathi M, Zareh Karizi S, Mohamadnia A. Expression of CK19-mRNA and CEA-mRNA biomarkers in pleural fluid of patients with non-small cell lung cancer. Minerva Pneumol 2017; 56(2): 78-83.
  16. Benedikova A, Srovnal J, Szkorupa M, Skalicky P, Chudacek J, Bohanes T, et al. Biomarkers in the detection of minimal systemic dissemination in lung cancer patients. Rozhl Chir 2012; 91(4): 209-15. [In Czech].
  17. Kutun S, Celik A, Cem KM, Erkorkmaz U, Eroglu A, Cetin A, et al. Expression of CK-19 and CEA mRNA in peripheral blood of gastric cancer patients. Exp Oncol 2010; 32(4): 263-8.
  18. Karimi S, Bahrami N, Sharifi K, Daustany M, Baghbani-Arani F, Kazempour M, et al. Investigating gene expression level of MUC1 and CEA in pleural fluid of NSCLC lung cancer patients with real-time RT-PCR method. Minerva Pneumol 2017; 56(1): 18-24.
  19. Zehentner BK, Dillon DC, Jiang Y, Xu J, Bennington A, Molesh DA, et al. Application of a multigene reverse transcription-PCR assay for detection of mammaglobin and complementary transcribed genes in breast cancer lymph nodes. Clin Chem 2002; 48(8): 1225-31.
  20. Bahrami N, Gholami M, Jamaati HR, Mohamadnia A, Dargahi H, Kazempour Dizaji M, et al. Expression of two essential mRNA biomarker in the peripheral blood as possible biomarkers for diagnosis of non-small cell lung carcinoma. Minerva Pneumol 2016; 55(3):31-6.
  21. Ghadimi K, Bahrami N, Fathi M, Farzanegan B, Naji T, Emami M, et al. Diagnostic value of LunX mRNA and CEA mRNA expression in pleural fluid of patients with non-small cell lung cancer. Minerva Pneumol 2017; 56(2): 90-5.
  22. Alvero AB, Burtness BA, Ercan AG, Sapi E. Improved method for the detection of cytokeratin 19-positive cells in the peripheral blood of breast cancer patients. Lab Invest 2004; 84(5): 658-61.
  23. Bilchik A, Miyashiro M, Kelley M, Kuo C, Fujiwara Y, Nakamori S, et al. Molecular detection of metastatic pancreatic carcinoma cells using a multimarker reverse transcriptase-polymerase chain reaction assay. Cancer 2000; 88(5): 1037-44.
  24. Andergassen U, Kolbl AC, Hutter S, Friese K, Jeschke U. Detection of circulating tumour cells from blood of breast cancer patients via RT-qPCR. Cancers (Basel) 2013; 5(4): 1212-20.
  25. Luo M, Hou L, Li J, Shao S, Huang S, Meng D, et al. VEGF/NRP-1axis promotes progression of breast cancer via enhancement of epithelial-mesenchymal transition and activation of NF-kappaB and beta-catenin. Cancer Lett 2016; 373(1): 1-11.
  26. Akbari A, Razzaghi Z, Homaee F, Khayamzadeh M, Movahedi M, Akbari ME. Parity and breastfeeding are preventive measures against breast cancer in Iranian women. Breast Cancer 2011; 18(1): 51-5.
  27. Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS. Cancer biomarkers - current perspectives. Indian J Med Res 2010; 132: 129-49.
  28. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002; 3(6): 415-28.
  29. Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle 2007; 6(12): 1455-9.
  30. Li J, Hu YM, Du YJ, Zhu LR, Qian H, Wu Y, et al. Expressions of MUC1 and vascular endothelial growth factor mRNA in blood are biomarkers for predicting efficacy of gefitinib treatment in non-small cell lung cancer. BMC Cancer 2014; 14: 848.
  31. Cesario A, Ferri L, Galetta D, Cardaci V, Biscione G, Pasqua F, et al. Pre-operative pulmonary rehabilitation and surgery for lung cancer. Lung Cancer 2007; 57(1): 118-9.
  32. Yan L, Yao Y, Wang LH, Wang ML, Fu XH. Detection of CK19, LUNX, and KS1/4 mRNA expression in the peripheral blood for diagnosis of micrometastases in patients with non-small cell lung cancer and their clinical implications. Genet Mol Res 2015; 14(4): 15090-5.
  33. Wang WB, Cui YG, Yao SY. Message RNA expression of LUNX, CK19 and CEA genes in NSCLC with micrometastasis in lymph nodes. Zhonghua Zhong Liu Za Zhi 2008; 30(2): 121-4. [In Chinese].
Journal of Isfahan Medical School
Volume 35, Issue 441 - Serial Number 441
July and August 2017
Pages 934-939

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History

  • Receive Date: 01 July 2017
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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