The Prediction Of Epidermal Growth Factor Receptor Mutation And Prognosis Of EGFR Tyrosine Kinase Inhibitor By Serum Ferritin In Advanced NSCLC

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Oct 22

PMID 31632143

Citations 5

Authors

Zhen Wu

Yu Dai

Liang-An Chen

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the association between level of serum ferritin (SF) and epidermal growth factor receptor (EGFR) mutations and to analyse the impact of SF level on survival times in advanced non-small-cell lung cancer (NSCLC) patients taking EGFR tyrosine kinase inhibitors (EGFR-TKIs).

Methods: A total of 301 patients who were admitted to the Chinese PLA general hospital from August 2015 to August 2017 were enrolled. The association between tumour markers, including SF, CEA, and EGFR mutation, and their impact on the prognosis of patients taking EGFR-TKIs was investigated.

Results: In all patients, the percentage of patients with EGFR mutations was 52.5% (158/301). EGFR mutations were more likely to be detected in younger (<60 years old), adenocarcinoma patients, non-smokers, women, CEA≥5 µg/L and serum ferritin ≥129 µg/L for females or ≥329 µg/L for males (<0.05). Increased serum ferritin was an independent factor for predicting EGFR mutations (odds ratio (OR)=4.593, 95% CI (2.673-7.890); <0.001), and an area under curve (AUC) of 0.711 was shown to predict EGFR mutations with a sensitivity of 81.7% and a specificity of 65.2% in women. Sensitivity increased to 91.1% when combining SF and CEA in all patients. SF was also an independent factor (HR=3.531, 95% CI (2.288-5.448); <0.001) for predicting progression-free survival (PFS) of patients on EGFR-TKIs, analysed by a Cox proportional hazard model, as PFS was shorter in patients with higher SF (15.0 mo. (SF < 129 µg/L for females or <329 for males) vs 10.0 mo. (129-258 µg/L for females or 329-658 µg/L for males) vs 7.3 mo. (>258 µg/L (>258 µg/L for females or >658 µg/L for males) p<0.001).

Conclusion: SF was a significant predictor of EGFR mutation with moderate diagnostic accuracy, and combining SF and CEA increased the diagnostic sensitivity and specificity for EGFR mutations. SF was also useful for predicting survival in EGFR-TKIs.

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References

Mayo C, Ortega F, Gimenez-Capitan A, Molina-Vila M, Serrano M, Viteri S . CK-coated magnetic-based beads as a tool to isolate circulating tumor cells (CTCs) in human tumors. Transl Lung Cancer Res. 2015; 2(2):65-71. PMC: 4369853. DOI: 10.3978/j.issn.2218-6751.2013.02.06. View

Mok T, Wu Y, Thongprasert S, Yang C, Chu D, Saijo N . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10):947-57. DOI: 10.1056/NEJMoa0810699. View

Gao Y, Song P, Li H, Jia H, Zhang B . Elevated serum CEA levels are associated with the explosive progression of lung adenocarcinoma harboring EGFR mutations. BMC Cancer. 2017; 17(1):484. PMC: 5512835. DOI: 10.1186/s12885-017-3474-3. View

Chinen L, Machado de Carvalho F, Rocha B, Aguiar C, Abdallah E, Campanha D . Cytokeratin-based CTC counting unrelated to clinical follow up. J Thorac Dis. 2013; 5(5):593-9. PMC: 3815714. DOI: 10.3978/j.issn.2072-1439.2013.09.18. View

Shoji F, Yoshino I, Yano T, Kometani T, Ohba T, Kouso H . Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas. Cancer. 2007; 110(12):2793-8. DOI: 10.1002/cncr.23101. View

Cai Z . Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients. Onco Targets Ther. 2016; 9:3873-8. PMC: 4930226. DOI: 10.2147/OTT.S102199. View

Shi Y, Au J, Thongprasert S, Srinivasan S, Tsai C, Khoa M . A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014; 9(2):154-62. PMC: 4132036. DOI: 10.1097/JTO.0000000000000033. View

Xu C, Zhou Q, Wu Y . Can EGFR-TKIs be used in first line treatment for advanced non-small cell lung cancer based on selection according to clinical factors? - A literature-based meta-analysis. J Hematol Oncol. 2012; 5:62. PMC: 3507915. DOI: 10.1186/1756-8722-5-62. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

10.

Shaozhang Z, Ming Z, Haiyan P, Aiping Z, Qitao Y, Xiangqun S . Comparison of ARMS and direct sequencing for detection of EGFR mutation and prediction of EGFR-TKI efficacy between surgery and biopsy tumor tissues in NSCLC patients. Med Oncol. 2014; 31(5):926. DOI: 10.1007/s12032-014-0926-3. View

11.

Zhi Q, Wang Y, Wang X, Yue D, Li K, Jiang R . Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma. Oncotarget. 2016; 7(40):64798-64809. PMC: 5323117. DOI: 10.18632/oncotarget.11703. View

12.

Han J, Li Y, Cao S, Dong Q, Zhao G, Zhang X . The level of serum carcinoembryonic antigen is a surrogate marker for the efficacy of EGFR-TKIs but is not an indication of acquired resistance to EGFR-TKIs in NSCLC patients with EGFR mutationsm. Biomed Rep. 2017; 7(1):61-66. PMC: 5492672. DOI: 10.3892/br.2017.914. View

13.

Okamoto T, Nakamura T, Ikeda J, Maruyama R, Shoji F, Miyake T . Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer. Eur J Cancer. 2005; 41(9):1286-90. DOI: 10.1016/j.ejca.2005.03.011. View

14.

Zhou C, Wu Y, Chen G, Feng J, Liu X, Wang C . Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011; 12(8):735-42. DOI: 10.1016/S1470-2045(11)70184-X. View

15.

Wang B, Zhang J, Song F, Tian M, Shi B, Jiang H . EGFR regulates iron homeostasis to promote cancer growth through redistribution of transferrin receptor 1. Cancer Lett. 2016; 381(2):331-40. DOI: 10.1016/j.canlet.2016.08.006. View

16.

Yildirim A, Meral M, Kaynar H, Polat H, Yilmazel Ucar E . Relationship between serum levels of some acute-phase proteins and stage of disease and performance status in patients with lung cancer. Med Sci Monit. 2007; 13(4):CR195-200. View

17.

Wang Z, Cheng Y, An T, Gao H, Wang K, Zhou Q . Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial. Lancet Respir Med. 2018; 6(9):681-690. DOI: 10.1016/S2213-2600(18)30264-9. View

18.

Kappers I, Vollebergh M, van Tinteren H, Korse C, Nieuwenhuis L, Bonfrer J . 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. 2012; 4:178. PMC: 3234018. DOI: 10.3332/ecancer.2010.178. View

19.

Taguchi F, Solomon B, Gregorc V, Roder H, Gray R, Kasahara K . Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst. 2007; 99(11):838-46. DOI: 10.1093/jnci/djk195. View

20.

Fidler M, Fhied C, Roder J, Basu S, Sayidine S, Fughhi I . The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients. BMC Cancer. 2018; 18(1):310. PMC: 5861613. DOI: 10.1186/s12885-018-4193-0. View