Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Serum α-1 Acid Glycoprotein is a Biomarker for the Prediction of Targeted Therapy Resistance in Advanced EGFR-positive Lung Adenocarcinoma

Author(s): Yu-Fen Xu, Yao Xu, Xia Li and Xin-Mei Yang*

Volume 21, Issue 10, 2018

Page: [755 - 759] Pages: 5

DOI: 10.2174/1386207322666190119163024

Price: $65

Abstract

Objective: To determine the levels of α-1 acid glycoprotein (ORM1) in the sera of advanced lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor (EGFR) mutation before treatment and after acquirement of EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance, and to explore the clinical cut off value of ORM1 for targeted therapy resistance in LUAD.

Methods: Enzyme-linked immunosorbent assay was used to determine serum ORM1 levels. Receiver operating characteristic curve was applied to evaluate the serum ORM1 level in the resistance of EGFR-TKI and the cut off value of ORM1 for the diagnosis of EGFR-TKI resistance.

Results: The serum ORM1 concentrations in the healthy group, before and after drug resistance were 1.687 ± 0.103, 1.868 ± 0.101, and 1.731 ± 0.088 µg/ml, respectively. The serum ORM1 concentrations before and after drug resistance were higher than that of the healthy group, whereas the serum ORM1 concentrations in the resistant group were lower than those before drug treatment. In comparison to healthy group, the area under curve (AUC) of the serum ORM1 concentration was 0.918 ± 0.029 with sensitivity of 90.5% and specificity of 78.6% in the patient before EGFR-TKI treatment, while the AUC was 0.644 ± 0.062 with sensitivity of 69.0% and specificity of 66.7% in the resistance group. When compared to those before treatment, the AUC of serum ORM1 concentration was 0.880 ± 0.038 with a sensitivity of 92.9% and specificity of 73.8% in the resistance group. The cutoff value of serum ORM1 was 1.778 µg/ml for advanced EGFR-positive LUAD and 1.723 µg/ml after resistance to EGFR-TKI.

Conclusion: Serum ORM1 has an important diagnostic value for the diagnosis of EGFR-positive LUAD and EGFR-TKI resistance in patients especially with advanced EGFR-positive LUAD. Our findings suggest that serum ORM1 is a biomarker in the prediction of EGFR-TKI resistance in EGFR-positive LUAD.

Keywords: ROC curve, lung adenocarcinoma, EGFR-TKI resistance, α-1 acid glycoprotein, biomarker, inhibitors.

« Previous Next »
[1]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[2]
Yi, H.G.; Kim, H.J.; Kim, Y.J.; Han, S.W.; Oh, D.Y.; Lee, S.H.; Kim, D.W.; Im, S.A.; Kim, T.Y.; Kim, C.S.; Heo, D.S.; Bang, Y.J. Epidermal growth factor receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer, 2009, 65(1), 80-84.
[3]
Zhou, C.; Wu, Y.L.; Chen, G.; Feng, J.; Liu, X.Q.; Wang, C.; Zhang, S.; Wang, J.; Zhou, S.; Ren, S.; Lu, S.; Zhang, L.; Hu, C.; Hu, C.; Luo, Y.; Chen, L.; Ye, M.; Huang, J.; Zhi, X.; Zhang, Y.; Xiu, Q.; Ma, J.; Zhang, L.; You, 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), 735-742.
[4]
Petrelli, F.; Borgonovo, K.; Cabiddu, M.; Barni, S. Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer: A pooled analysis of three randomized trials. Anticancer Drugs, 2011, 22(10), 1010-1019.
[5]
Suda, K.; Mizuuchi, H.; Maehara, Y.; Mitsudomi, T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny. Cancer Metastasis Rev., 2012, 31(3-4), 807-814.
[6]
Rosell, R.; Carcereny, E.; Gervais, R.; Vergnenegre, A.; Massuti, B.; Felip, E.; Palmero, R.; Garcia-Gomez, R.; Pallares, C.; Sanchez, J.M.; Porta, R.; Cobo, M.; Garrido, P.; Longo, F.; Moran, T.; Insa, A.; De Marinis, F.; Corre, R.; Bover, I.; Illiano, A.; Dansin, E.; de Castro, J.; Milella, M.; Reguart, N.; Altavilla, G.; Jimenez, U.; Provencio, M.; Moreno, M.A.; Terrasa, J.; Muñoz-Langa, J.; Valdivia, J.; Isla, D.; Domine, M.; Molinier, O.; Mazieres, J.; Baize, N.; Garcia-Campelo, R.; Robinet, G.; Rodriguez-Abreu, D.; Lopez-Vivanco, G.; Gebbia, V.; Ferrera-Delgado, L.; Bombaron, P.; Bernabe, R.; Bearz, A.; Artal, A.; Cortesi, E.; Rolfo, C.; Sanchez-Ronco, M.; Drozdowskyj, A.; Queralt, C.; de Aguirre, I.; Ramirez, J.L.; Sanchez, J.J.; Molina, M.A.; Taron, M.; Paz-Ares, L. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol., 2012, 13(3), 239-246.
[7]
Bruno, R.; Olivares, R.; Berille, J.; Chaikin, P.; Vivier, N.; Hammershaimb, L.; Rhodes, G.R.; Rigas, J.R. Alpha-1-acid glycoprotein as an independent predictor for treatment effects and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel. Clin. Cancer Res., 2003, 9(3), 1077-1082.
[8]
Kasprzyk, M.; Dyszkiewicz, W.; Zwaruń, D.; Leśniewska, K.; Wiktorowicz, K. The assessment of acute phase proteins as prognostic factors in patients surgically treated for non-small cell lung cancer. Pneumonol. Alergol. Pol., 2008, 76(5), 321-326.
[9]
Jackman, D.; Pao, W.; Riely, G.J.; Engelman, J.A.; Kris, M.G.; Jänne, P.A.; Lynch, T.; Johnson, B.E.; Miller, V.A. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J. Clin. Oncol., 2010, 28(2), 357-360.
[10]
Mu, X.L.; Li, L.Y.; Zhang, X.T.; Wang, M.Z.; Feng, R.E.; Cui, Q.C.; Zhou, H.S.; Guo, B.Q. Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in chinese patients with non-small cell lung cancer. Clin. Cancer Res., 2005, 11(12), 4289-4294.
[11]
Fukuoka, M.; Wu, Y.L.; Thongprasert, S.; Sunpaweravong, P.; Leong, S.S.; Sriuranpong, V.; Chao, T.Y.; Nakagawa, K.; Chu, D.T.; Saijo, N.; Duffield, E.L.; Rukazenkov, Y.; Speake, G.; Jiang, H.; Armour, A.A.; To, K.F.; Yang, J.C.; Mok, T.S. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J. Clin. Oncol., 2011, 29(21), 2866-2874.
[12]
Hirsch, F.R.; Suda, K.; Wiens, J.; Bunn, P.A. Jr. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet, 2016, 388(10048), 1012-1024.
[13]
Chen, H.; Jin, S.; Pan, T.; Zhou, Z.; Liu, H.; Pang, H.; Gong, C.; Wang, L.; Wang, Y.; Shi, G.; Ge, H.; Bu, C.; Sun, X.; Zhang, R.; Fang, F. CT increases the evaluation of efficacy in the treatment of non - small cell lung cancer with ekotinib. Chin J. Gerontol., 2015, 5, 1216-1217.
[14]
Smith, A.D.; Shah, S.N.; Rini, B.I.; Lieber, M.L.; Remer, E.M. Morphology, Attenuation, Size, and Structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR Am. J. Roentgenol., 2010, 194(6), 1470-1478.
[15]
Choi, H.; Charnsangavej, C.; Faria, S.C.; Macapinlac, H.A.; Burgess, M.A.; Patel, S.R.; Chen, L.L.; Podoloff, D.A.; Benjamin, R.S. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: Proposal of new computed tomography response criteria. J. Clin. Oncol., 2007, 25(13), 1753-1759.
[16]
Shimada, Y.; Saji, H.; Yoshida, K.; Kakihana, M.; Honda, H.; Nomura, M.; Usuda, J.; Kajiwara, N.; Ohira, T.; Ikeda, N. Prognostic factors and the significance of treatment after recurrence in completely resected stage I non-small cell lung cancer. Chest, 2013, 143(6), 1626-1634.
[17]
Huang, L.J.; Chen, S.X.; Huang, Y.; Luo, W.J.; Jiang, H.H.; Hu, Q.H.; Zhang, P.F.; Yi, H. Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer. Lung Cancer, 2006, 54(1), 87-94.
[18]
Zsila, F.; Fitos, I.; Bencze, G.; Kéri, G.; Orfi, L. Determination of human serum alpha1-acid glycoprotein and albumin binding of various marketed and preclinical kinase inhibitors. Curr. Med. Chem., 2009, 16(16), 1964-1977.
[19]
Israili, Z.H.; Dayton, P.G. Dayton, Human alpha-1-glycoprotein and its interactions with drugs. Drug Metab. Rev., 2001, 33(2), 161-235.
[20]
van Dijk, W.; Havenaar, E.C.; Brinkman-van der Linden, E.C. Brinkman-van der Linden, Alpha 1-acid glycoprotein (orosomucoid): Pathophysiological changes in glycosylation in relation to its function. Glycoconj. J., 1995, 12(3), 227-233.
[21]
Alexandrakis, M.G.; Coulocheri, S.A.; Bouros, D.; Vlachonikolis, I.G.; Eliopoulos, G.D. Significance of alpha-2-macroglobulin, alpha-1-acid glycoprotein, and C-reactive protein in pleural effusion differentiation. Respiration, 2000, 67(1), 30-35.
[22]
Fournier, T.; Medjoubi-N, N.; Porquet, D. Alpha-1-acid glycoprotein. Biochim. Biophys. Acta, 2000, 1482(1-2), 157-171.
[23]
Tanabe, K.; Kitagawa, K.; Kojima, N.; Iijima, S. Multifucosylated alpha-1-acid glycoprotein as a novel marker for hepatocellular carcinoma. J. Proteome Res., 2016, 15(9), 2935-2944.
[24]
Jabir, R.S.; Ho, G.F.; Annuar, M.A.B.A.; Stanslas, J. Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients. Biomarkers, 2018, 23(2), 142-146.
[25]
Duché, J.C.; Urien, S.; Simon, N.; Malaurie, E.; Monnet, I.; Barré, J. Expression of the genetic variants of human alpha-1-acid glycoprotein in cancer. Clin. Biochem., 2000, 33(3), 197-202.
[26]
Yildirim, A.; Meral, M.; Kaynar, H.; Polat, H.; Ucar, E.Y. 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-CR200.
[27]
Ayyub, A.; Saleem, M.; Fatima, I.; Tariq, A.; Hashmi, N.; Musharraf, S.G. Glycosylated Alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker. Int. J. Biochem. Cell Biol., 2016, 70, 68-75.

Rights & Permissions Print Cite
Article Metrics
52
4
1
© 2024 Bentham Science Publishers | Privacy Policy