DOI QR코드

DOI QR Code

Analysis of CEA Expression and EGFR Mutation Status in Non-small Cell Lung Cancers

  • Yang, Zhong-Ming ;
  • Ding, Xian-Ping ;
  • Pen, Lei ;
  • Mei, Lin ;
  • Liu, Ting
  • Published : 2014.04.30

Abstract

Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

Keywords

Carcinoembryonic antigen;EGF receptor;non-small cell lung cancer;tyrosine kinase inhibitor

References

  1. Tsai CM, Chen JT, Chiu CH, et al (2013). Combined epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor and chemotherapy in non-small-cell lung cancer: chemorefractoriness of cells harboring sensitizing-EGFR mutations in the presence of gefitinib. Lung Cancer, 82, 305-12. https://doi.org/10.1016/j.lungcan.2013.08.028
  2. Wang JF, Long H (2012). Relationship between epidermal growth factor receptor mutation and carcinoembryonic antigen expression level in non-small cell lung cancer. Guangdong Med J, 33, 1589-92.
  3. Yan HA, Shen K, Huang XE (2013).Clinical study on mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4801-4. https://doi.org/10.7314/APJCP.2013.14.8.4801
  4. Mok TS, Wu YL, Thongpraster S, et al (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 361, 947-57. https://doi.org/10.1056/NEJMoa0810699
  5. Lu YY, Huang XE, Xu L, et al (2013).Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs. Asian Pac J Cancer Prev, 14, 2005-8. https://doi.org/10.7314/APJCP.2013.14.3.2005
  6. McFarlane ME, Plummer JM, Bonadie K (2013). Mucinous cystadenoma of the appendix presenting with an elevated carcinoembryonic antigen (CEA): Report of two cases and review of the literature. Int J Surg Case Rep, 4, 886-8. https://doi.org/10.1016/j.ijscr.2013.07.007
  7. Miller VA, Riely GJ, Zakowski MF, et al (2008). Molecular characteristics of bronchioloalveolar carcinoma and aden ocarcinoma,bronchioloalveolar carcinoma subtype,predict response to erlotinib. J Clin Oncol, 26, 1472-8. https://doi.org/10.1200/JCO.2007.13.0062
  8. Ordoñez C, Screaton RA, Ilantzis C, et al (2000). Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Res, 60, 3419- 24.
  9. Sequist LV, Joshi VA, Janne PA, et al (2007). Response to treatment and survival of patients with non-samall cell lung cancer undergoing somatic EGFR mutation testing. Oncologist, 12, 90-8. https://doi.org/10.1634/theoncologist.12-1-90
  10. Sequist LV, Martins RG, Spigel D, et al (2008). First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutation. J Clin Oncol, 26, 2442-9. https://doi.org/10.1200/JCO.2007.14.8494
  11. Sisto M, Lisi S, D'Amore M, et al (2014). The metalloproteinase ADAM17 and the epidermal growth factor receptor (EGFR) signaling drive the inflammatory epithelial response in Sjögren's syndrome. Clin Exp Med, [Epub ahead of print].
  12. Sordella R, Bell DW, Haber DA, et al (2004). Gefitinibsensitizing EGFR mutations in lung cancer activate antiapoptotic pathways. Science, 305, 1163-7. https://doi.org/10.1126/science.1101637
  13. Kobayashi M, Takeuchi T, Ohtsuki Y (2008). Establishment of three novel human malignant pleural mesothelioma cell lines: morphological and cytogenetical studies and EGFR mutation status. Anticancer Res, 28, 197-208.
  14. Ji H, Li D, Chen L, et al (2006). The impact of human EGFR kinase domain mutation on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell, 9, 485-95. https://doi.org/10.1016/j.ccr.2006.04.022
  15. Ji ZQ, Liu J, Wu XY, et al (2014). Basic and Clinical investigation of Yadazi and Banmao combined with chemotherapy in treating patients with lung cancer. Int J Med Res Clin Oncol, 1, 16-20.
  16. Kappers I, Vollebergh MA, van Tinteren H, et al (2010). Soluble epidermal growth factor receptor (sEGFR) and carcinoembryonic antigen (CEA) concentration in patients with non-small cell lung cancer: correlation with survival after erlotinib and gefitinib treatment. Ecancermedicalscience, 4, 178.
  17. Li CG, Huang XE, Xu L, et al (2012).Clinical application of serum tumor associated material (TAM) from non-small cell lung cancer patients. Asian Pac J Cancer Prev, 13, 301-4. https://doi.org/10.7314/APJCP.2012.13.1.301
  18. Liam CK, Leow HR, How SH, et al (2014). Epidermal growth factor receptor mutations in non- small cell lung cancers in a multiethnic malaysian patient population. Asian Pac J Cancer Prev, 15, 321-6. https://doi.org/10.7314/APJCP.2014.15.1.321
  19. Lim SH, Lee JY, Sun JM, et al (2014). Comparison of clinical outcomes following gefitinib and erlotinib treatment in non-small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21. J Thorac Oncol, 9, 506-11. https://doi.org/10.1097/JTO.0000000000000095
  20. Liu YC, Zhou SB, Gao F, et al (2013).Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  21. Finberg KE, Sequist LV, Joshi VA, et al (2007). Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcionmas with bronchioloaveolar features. J Mol Diagn, 9, 320-6. https://doi.org/10.2353/jmoldx.2007.060182
  22. Cui L, Liu XX, Jiang Y, et al (2014).Phase II study on dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 1699-702. https://doi.org/10.7314/APJCP.2014.15.4.1699
  23. Duffy MJ, van Dalen A, Haglund C, et al (2003). Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer, 39, 718-27. https://doi.org/10.1016/S0959-8049(02)00811-0
  24. Fei ZH, Yao CY, Yang XL, et al (2013).Serum BMP-2 upregulation as an indicator of poor survival in advanced non-small cell lung cancer patients. Asian Pac J Cancer Prev, 14, 5293-9. https://doi.org/10.7314/APJCP.2013.14.9.5293
  25. Fukuoka M, Wu YL, Thongprasert S, et al (2011). Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study ofgefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer inAsia (IPASS). J Clin Oncol, 29, 2866-74. https://doi.org/10.1200/JCO.2010.33.4235
  26. Hirsh FR, Bunn PA, Jr (2009). EGFR testing in lung cancer is ready for prime time. Lancet Oncol, 10, 432-3. https://doi.org/10.1016/S1470-2045(09)70110-X
  27. Hsiao SH, Liu HE, Lee HL, et al (2013). Distinct clinical outcomes of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors: non-responders versus responders. PLoS One, 8, e83266. https://doi.org/10.1371/journal.pone.0083266
  28. Janssens A, Droogh E, Lefebure A, et al (2014). Routine implementation of EGFR mutation testing in clinical practice in Flanders: 'HERMES' project. Acta Clin Belg, 69, 92-7. https://doi.org/10.1179/0001551214Z.00000000029
  29. Bordi P, Tiseo M, Bortesi B, et al (2014). Overcoming T790Mdriven acquired resistance to EGFR-TKIs in NSCLC with afatinib: a case report. Tumori, 100, e20-3.

Cited by

  1. Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods vol.15, pp.21, 2014, https://doi.org/10.7314/APJCP.2014.15.21.9367
  2. Frequency of EGFR Mutations in Non-small Cell Lung Cancer Patients: Screening Data from West Siberia vol.16, pp.2, 2015, https://doi.org/10.7314/APJCP.2015.16.2.689
  3. Factors associated with efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer vol.39, pp.5, 2017, https://doi.org/10.1177/1010428317705340