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Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer

  • Original Article – Cancer Research
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Abstract

Purpose

Signalling through the insulin-like growth factor 1 receptor (IGF-1R) is implicated in carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. The purpose of this study was to investigate the prognostic role of IGF-1R expression in surgically resected non-small-cell lung cancer (NSCLC), and responses to IGF-1R tyrosine kinase inhibitor NVP-ADW742 in a panel of lung cancer cell lines.

Methods

Insulin-like growth factor 1 receptor (IGF-1R) expression was evaluated by quantitative RT-PCR in 115 NSCLC samples and in a panel of 6 NSCLC cell lines. Cytotoxicity experiments with IGF-1R inhibitor and conventional systemic drugs such as paclitaxel in cell lines were realised.

Results

Insulin-like growth factor 1 receptor (IGF-1R) was differentially expressed across histologic subtypes, with the lowest levels observed in squamous cell tumours. Median survival was longer in patients with squamous tumour histology expressing low IGF-1R levels. In multivariable analysis, ageing and high tumour stage were significant predictors of worse overall survival. The hazard of death was lower in patients with squamous histology and low IGF-1R gene expression. There was no correlation between IGF-1R expression and response to tyrosine kinase inhibitor in cell lines tested. However, combination drug treatment resulted in synergistically enhanced antiproliferative effects on several cell lines.

Conclusions

These findings suggest that IGF-1R is a potential target for therapy in NSCLC patients. Combination therapies will have an important role in treatment.

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Acknowledgments

This work was supported by Fundación Médica Mutua Madrileña (Madrid, Spain) Grant 2008/107. MTAO is supported by Instituto de Salud Carlos III (FIS CM 06/00231) and Spanish Association Against Cancer (AECC, PAO 2009), VDG by Fundación Mutua Madrileña 2010/0018, Spain, AAL by RTICC (Red Temática de Investigación Cooperativa de Cáncer, ISCIII, Spain), and CP by Ministerio de Sanidad y Política Social. TRA-151 (Spain). The authors thank Dr. JC Rubio (Genomic Laboratory, Instituto de Investigación Hospital 12 de Octubre, Madrid) for his support with qRT-PCR analysis tolls and mutational experiments.

Conflict of interest

The authors disclosed no potential conflict of interests.

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Author notes

  1. Ana Cortijo

    Present address: Clinical Research Support Office, MD Anderson Cancer Center, Calle Arturo Soria 270, 28033, Madrid, Spain

Authors and Affiliations

  1. Translational Oncology, Instituto de Investigación Hospital 12 de Octubre (i+12), Avda de Córdoba S/N, 28041, Madrid, Spain

    M. Teresa Agulló-Ortuño, C. Vanesa Díaz-García, Alba Agudo-López, Carlos Pérez, Hernán Cortés-Funes & José A. López Martín

  2. Oncology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba S/N, 28041, Madrid, Spain

    Ana Cortijo, Hernán Cortés-Funes & José A. López Martín

  3. Oncology Department, Hospital Universitario Virgen del Rocío, Avda de Manuel Siurot S/N, 41013, Sevilla, Spain

    Luis Paz-Ares

  4. Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico Clara Campal, Hospital Universitario Madrid-Sanchinarro, Calle Oña 10, 28050, Madrid, Spain

    Fernando López-Ríos

  5. Pneumology Department, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES-ISCIII), Hospital Universitario 12 de Octubre, Avda de Córdoba S/N, 28041, Madrid, Spain

    Francisco Pozo

  6. Oncology Department, Hospital Universitario La Paz, Paseo de La Castellana 261, 28046, Madrid, Spain

    Javier de Castro

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  1. M. Teresa Agulló-Ortuño
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Correspondence to José A. López Martín.

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Agulló-Ortuño, M.T., Díaz-García, C.V., Agudo-López, A. et al. Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer. J Cancer Res Clin Oncol 141, 43–53 (2015). https://doi.org/10.1007/s00432-014-1787-z

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