DOI QR코드

DOI QR Code

Cell Free EGFR mRNA Expression and Implications for Survival and Metastasis in Non-Small Cell Lung Cancer Cases

  • Masroor, Mirza (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals) ;
  • Mir, Rashid (Faculty of Applied Medical Sciences, University of Tabuk) ;
  • Javid, Jamsheed (Faculty of Applied Medical Sciences, University of Tabuk) ;
  • Prasant, Y (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals) ;
  • Imtiyaz, A (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals) ;
  • Mariyam, Z (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals) ;
  • Mohan, Anant (Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences) ;
  • Ray, PC (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals) ;
  • Saxena, Alpana (Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals)
  • Published : 2015.10.06

Abstract

Background: NSCLC is a disease involving uncontrolled cell growth, which could result in metastases into nearby tissues beyond the lungs. Materials and Methods: The aim of the present study was to analyze the influence of epidermal growth factor receptor (EGFR) gene expression on metastasis and survival in NSCLC patients. The present case-control study included 100 cases of NSCLC patients and 100 age and sex matched controls. EGFR gene expression was analyzed by quantitative real time PCR using serum RNA. Association with NSCLC patient survival was analyzed by the Kaplan-Meier method. Results: We analyzed EGFR gene expression and observed mean increased gene expression of 13.5 fold in NSCLC patients. Values reflected overall survival of patients with a median of 15.8 months in the cases of <13 fold increased gene expression vs 6.7 months with >13 fold increased EGFR gene expression (p=0.005). Distant metastatic patients with <13 fold increased EGFR gene expression had 7.9 months of median survival time while>13 fold increased EGFR gene expression had only 5 months of median survival time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene expression had 18 months of median survival time as compared to only 7.1 months with >13 fold increased expression. Conclusions: Higher cell free EGFR mRNA expression may play an important role in causing distant metastases and reducing overall survival of NSCLC patients in the Indian population.

Keywords

References

  1. Atmaca A, Werner D, Pauligk C, et al (2012). The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer. BMC Cancer, 12, 524. https://doi.org/10.1186/1471-2407-12-524
  2. Bloomston M, Bhardwaj A, Ellison EC, et al (2006). Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg, 23, 74-9. https://doi.org/10.1159/000093497
  3. Dowell JE, Minna JD (2005). Chasing mutations in the epidermal growth factor in lung cancer. N Engl J Med, 352, 830-2. https://doi.org/10.1056/NEJMe058033
  4. Engelman JA, Janne PA, Mermel C, et al (2005). ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinibsensitive nonsmall cell lung cancer cell lines. Proc Natl Acad Sci U S A, 102, 3788-93. https://doi.org/10.1073/pnas.0409773102
  5. Franklin WA, Veve R, Hirsch FR, et al (2002). Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol, 29, 3-14. https://doi.org/10.1053/sonc.2002.35642
  6. Ge H, Gong X, Tang CK (2002). Evidence of high incidence of EGFRvIII expression and co-expression with EGFR in human invasive breast cancer by laser capture microdissection and immunohistochemical analysis. Int J Cancer, 98, 357-61. https://doi.org/10.1002/ijc.10224
  7. Gschwind A, Fischer OM, Ullrich A (2004). The discovery of receptor tyrosine kinases: targets for cancer therapy. Nature Rev Cancer, 4, 361-70. https://doi.org/10.1038/nrc1360
  8. Hayes DC, Secrist H, Bangur CS, et al (2006). Multigene realtime PCR detection of circulating tumor cells in peripheral blood of lung cancer patients. Anticancer Res, 26, 1567-75.
  9. Hirsch FR, Varella-Garcia M, Capuzzo (2009). Predictive value of EGFR and HER2 overexpression in advanced non-smallcell lung cancer. Oncogene, 28, 32-7. https://doi.org/10.1038/onc.2009.199
  10. Hirsch FR, Varella-Garcia M, Franklin WA, et al (2002). Evaluation of HER2/ neu in non-small cell lung cancer by immunohistochemistry and fluorescence in-situ hybridization (FISH) techniques. Br J Cancer, 86, 1449-56. https://doi.org/10.1038/sj.bjc.6600286
  11. H J Lee, A N Seo, E J Kim et al (2014). Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer. British J Cancer, 112, 103-11.
  12. Hynes NE, Lane HA (2005). ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer, 5, 341-54. https://doi.org/10.1038/nrc1609
  13. Inamura K, Ninomiya H, Ishikawa Y, et al (2010). Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features? Arch Pathol Lab Med, 134, 66-72.
  14. Ivan Bieche, Peter Onody, Sengul Tozlu, et al (2003). Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer, 106, 758-65. https://doi.org/10.1002/ijc.11273
  15. Lewis SZ, Diekemper R, Addrizzo Harris DJ (2013). Methodology for development of guidelines for lung cancer: diagnosis and management of lung cancer, 3rd ed: american college of chest physicians evidence-based clinical practice guidelines. Chest, 143, 41-50. https://doi.org/10.1378/chest.12-2344
  16. Masuda H, Zhang D, Bartholomeusz C, et al (2012) Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat, 136, 331-45. https://doi.org/10.1007/s10549-012-2289-9
  17. Qing Li, Yongfeng Tang, Xue Cheng, et al (2014). EGFR protein expression and gene amplification in squamous intraepithelial lesions and squamous cell carcinomas of the cervix. Int J Clin Exp Pathol, 7, 733-41.
  18. Quesnelle KM, Boehm AL, Grandis JR (2007). STAT-mediated EGFR signaling in cancer. J Cell Biochem, 102, 311-9. https://doi.org/10.1002/jcb.21475
  19. Riese D J, Stern DF, (1998). Specificity within the EGF family/ErbB receptor family signaling network. Bioessays, 20, 41-8. https://doi.org/10.1002/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V
  20. Salomon DS, Brandt R, Ciardiello F, et al (1995). Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol, 19, 183-232. https://doi.org/10.1016/1040-8428(94)00144-I
  21. Scagliotti GV, Selvaggi G, Novello S, et al (2004). The biology of epidermal growth factor receptor in lung cancer. Clin Cancer Res, 10, 4227-32. https://doi.org/10.1158/1078-0432.CCR-040007
  22. Schlessinger J (2004). Common and distinct elements in cellular signaling via EGF and FGF receptors. Science, 306, 1506- 07. https://doi.org/10.1126/science.1105396
  23. Sekido Y, Fong KM, Minna JD, (2003) Molecular genetics of lung cancer. Annu Rev Med, 54, 73-87. https://doi.org/10.1146/annurev.med.54.101601.152202
  24. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  25. Tobita K, Kijima H, Dowaki S, et al (2003). Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastases. Int J Mol Med, 11, 305-9.
  26. Travis WD, Brambilla E, Noguchi M, et al (2013). Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 international association for the study of lung cancer/american thoracic society/european respiratory society classification. Arch Pathol Lab Med, 137, 668-84. https://doi.org/10.5858/arpa.2012-0263-RA
  27. Utsugi T (2013). New challenges and inspired answers for anticancer drug discovery and development. Jpn J Clin Oncol, 43, 945-53. https://doi.org/10.1093/jjco/hyt131
  28. Wang X, Zhang S, MacLennan GT, et al (2007). Epidermal growth factor receptor protein expression and gene amplification, in small cell carcinoma of the urinary bladder. Clin Cancer Res, 13, 953-7. https://doi.org/10.1158/1078-0432.CCR-06-2167
  29. Wang X, Zhang S, MacLennan GT, et al (2008). Epidermal growth factor receptor protein expression and gene amplification in the chemorefractory metastatic embryonal carcinoma. Mod Pathol, 22, 7-12.
  30. World Health Organization (2012). Cancer fact sheet. http://www.who.int/mediacentre/factsheets/ fs297/en/.
  31. Xu W, Yang G, Xu Y, et al (2014). The possibility of traditional chinese medicine as maintenance therapy for advanced nonsmall cell lung cancer. Evid Based Complement Alternat Med,. 2014, 278917.
  32. Yarden Y, Sliwkowski MX, (2001). Untangling the ErbB signalling network. Nature Rev Mol Cell Biol, 2, 127-37. https://doi.org/10.1038/35052073
  33. Zhang YJ, Gallis B, Taya M, et al (2013). pH-Responsive artemisinin derivatives and lipid nanoparticle formulations inhibit growth of breast cancer cells in vitro and in duce down-regulation of her family members. PLoS One, 8, 59086. https://doi.org/10.1371/journal.pone.0059086

Cited by

  1. Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/9792730