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Article

EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab

  • Authors:
    • Xiaohong Wang
    • Runjia Fu
    • Ying Hu
    • Hong Du
    • Shuangxi Li
    • Ziyu Li
    • Yiqiang Liu
    • Qixiang Li
    • Lianhai Zhang
    • Jiafu Ji
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, Crown Bioscience Inc., Light Muller Building, Changping Sector of Zhongguancun Science Park, Changping, Beijing 102200, P.R. China
  • Pages: 2387-2393
    |
    Published online on: August 14, 2017
       https://doi.org/10.3892/or.2017.5907
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Abstract

Cetuximab has been evaluated as a first-line treatment with conflicting results. The aim of the present study was to investigate the relationship between epidermal growth factor receptor (EGFR) status, and response and survival benefit following cetuximab treatment in gastric cancer (GC). Using 20 patient-derived GC xenograft (PDX) models, the mice (10 mice/model) were randomly assigned into two groups. The control group and treatment group were treated with PBS and cetuximab, respectively. The drug response was evaluated by monitoring tumor growth. Survival benefit was evaluated by comparing the survival curves corresponding to the time for the tumors to reach 600 mm3. Our results revealed that the PDX models treated with cetuximab had better survival than that noted for the non-treated group (P<0.05). The EGFR status was measured by FISH, qPCR, RNAish and immunohistochemistry, respectively. Four cases in the treated group were identified as responsive to cetuximab. EGFR mRNA and protein overexpression were associated with the response to cetuximab (P<0.05). EGFR amplification, mRNA and protein overexpression were associated with prolonged survival in the cetuximab-treated PDX models. Moreover, in the PDX models with EGFR amplification, mRNA or protein overexpression, cetuximab treatment was associated with a better survival compared with that noted in the untreated group in the PDX models (P<0.05), while the survival was not statistically different in the other cases (P>0.05). In conclusion, cetuximab provided survival benefit in the trial. The level of EGFR amplification and overexpression significantly predicted response and survival benefit, particularly the mRNA and protein expression level. A combination of mRNA and protein expression may predict efficacy of cetuximab more efficiently.
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1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Gomez-Martin C, Plaza JC, Pazo-Cid R, Salud A, Pons F, Fonseca P, Leon A, Alsina M, Visa L, Rivera F, et al: Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol. 31:4445–4452. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Luo HY, Wei W, Shi YX, Chen XQ, Li YH, Wang F, Qiu MZ, Li FH, Yan SL, Zeng MS, et al: Cetuximab enhances the effect of oxaliplatin on hypoxic gastric cancer cell lines. Oncol Rep. 23:1735–1745. 2010.PubMed/NCBI

4 

Pinto C, Di Fabio F, Siena S, Cascinu S, Llimpe Rojas FL, Ceccarelli C, Mutri V, Giannetta L, Giaquinta S, Funaioli C, et al: Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol. 18:510–517. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS, Lee NS, Lee KH, Choi IS, Lee MH, et al: Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer. 100:298–304. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Kim C, Lee JL, Ryu MH, Chang HM, Kim TW, Lim HY, Kang HJ, Park YS, Ryoo BY and Kang YK: A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Invest New Drugs. 29:366–373. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, et al: Arbeitsgemeinschaft Internistische Onkologie and EXPAND Investigators: Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial. Lancet Oncol. 14:490–499. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Higaki E, Kuwata T, Nagatsuma AK, Nishida Y, Kinoshita T, Aizawa M5, Nitta H, Nagino M and Ochiai A: Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: Evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method. Gastric Cancer. 19:63–73. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Hotz B, Keilholz U, Fusi A, Buhr HJ and Hotz HG: In vitro and in vivo antitumor activity of cetuximab in human gastric cancer cell lines in relation to epidermal growth factor receptor (EGFR) expression and mutational phenotype. Gastric Cancer. 15:252–264. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, et al: 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. 12:735–742. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: North-East Japan Study Group: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, et al: West Japan Oncology Group: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Mazières J, Brugger W, Cappuzzo F, Middel P, Frosch A, Bara I, Klingelschmitt G and Klughammer B: Evaluation of EGFR protein expression by immunohistochemistry using H-score and the magnification rule: Re-analysis of the SATURN study. Lung Cancer. 82:231–237. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Dahabreh IJ, Linardou H, Kosmidis P, Bafaloukos D and Murray S: EGFR gene copy number as a predictive biomarker for patients receiving tyrosine kinase inhibitor treatment: A systematic review and meta-analysis in non-small-cell lung cancer. Ann Oncol. 22:545–552. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Licitra L, Mesia R, Rivera F, Remenár E, Hitt R, Erfán J, Rottey S, Kawecki A, Zabolotnyy D, Benasso M, et al: Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol. 22:1078–1087. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Zhang L, Yang J, Cai J, Song X, Deng J, Huang X, Chen D, Yang M, Wery JP, Li S, et al: A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy. Sci Rep. 3:29922013. View Article : Google Scholar : PubMed/NCBI

17 

Washington K: 7th edition of the AJCC cancer staging manual: Stomach. Ann Surg Oncol. 17:3077–3079. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Yang M, Shan B, Li Q, Song X, Cai J, Deng J, Zhang L, Du Z, Lu J, Chen T, et al: Overcoming erlotinib resistance with tailored treatment regimen in patient-derived xenografts from naïve Asian NSCLC patients. Int J Cancer. 132:E74–84. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Julien S, Merino-Trigo A, Lacroix L, Pocard M, Goéré D, Mariani P, Landron S, Bigot L, Nemati F, Dartigues P, et al: Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res. 18:5314–5328. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Schleich N, Po C, Jacobs D, Ucakar B, Gallez B, Danhier F and Préat V: Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy. J Control Release. 194:82–91. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, et al: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): A randomised, open-label phase 3 trial. Lancet Oncol. 14:481–489. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Fox SB, Kumarasinghe MP, Armes JE, Bilous M, Cummings MC, Farshid G, Fitzpatrick N, Francis GD, McCloud PI, Raymond W, et al: Gastric HER2 Testing Study (GaTHER): An evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia. Am J Surg Pathol. 36:577–582. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Tang D, Liu CY, Shen D, Fan S, Su X, Ye P, Gavine PR and Yin X: Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas. Onco Targets Ther. 8:7–14. 2014.PubMed/NCBI

24 

Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, et al: Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 97:643–655. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, et al: Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 353:133–144. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Peled N, Yoshida K, Wynes MW and Hirsch FR: Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer. Ther Adv Med Oncol. 1:137–144. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Fu R, Hu Y, Du H, Li S, Li Z, Liu Y, Li Q, Zhang L, Ji J, Ji J, et al: EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab. Oncol Rep 38: 2387-2393, 2017.
APA
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z. ... Ji, J. (2017). EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab. Oncology Reports, 38, 2387-2393. https://doi.org/10.3892/or.2017.5907
MLA
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z., Liu, Y., Li, Q., Zhang, L., Ji, J."EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab". Oncology Reports 38.4 (2017): 2387-2393.
Chicago
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z., Liu, Y., Li, Q., Zhang, L., Ji, J."EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab". Oncology Reports 38, no. 4 (2017): 2387-2393. https://doi.org/10.3892/or.2017.5907
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Fu R, Hu Y, Du H, Li S, Li Z, Liu Y, Li Q, Zhang L, Ji J, Ji J, et al: EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab. Oncol Rep 38: 2387-2393, 2017.
APA
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z. ... Ji, J. (2017). EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab. Oncology Reports, 38, 2387-2393. https://doi.org/10.3892/or.2017.5907
MLA
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z., Liu, Y., Li, Q., Zhang, L., Ji, J."EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab". Oncology Reports 38.4 (2017): 2387-2393.
Chicago
Wang, X., Fu, R., Hu, Y., Du, H., Li, S., Li, Z., Liu, Y., Li, Q., Zhang, L., Ji, J."EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab". Oncology Reports 38, no. 4 (2017): 2387-2393. https://doi.org/10.3892/or.2017.5907
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