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Integrin ανβ6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis

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Abstract

Background and Objective

Integrins are a family of adhesion receptor proteins that provide signaling from the extracellular matrix to the cytoplasm. They have been associated with cancer by promoting migration, invasion, metastasis, and survival. ανβ6 integrin is upregulated in several tumors. Here, we evaluate the prognostic impact of ανβ6 integrin protein expression in solid tumors.

Methods

A systematic search of electronic databases identified publications exploring the effect of ανβ6 integrin on overall survival (OS). Hazard ratios (HRs) were pooled in a meta-analysis using generic inverse variance and random effects modeling. Subgroup analyses were conducted based on tumor site, tumor stage, antibody used for immunohistochemistry (IHC) and method for extraction of the HR. A meta-regression explored the influence of clinical variables on the magnitude of effect of ανβ6 integrins on OS.

Results

Seventeen studies comprising 5795 patients met the inclusion criteria. High ανβ6 integrin expression in tumors was associated with worse OS (HR 1.65, 95% confidence interval [CI] 1.32–2.06; Cochran’s Q p < 0.001, I2 = 81%). Adverse outcomes were similar in all tumor sites (subgroup difference p = 0.10), with the strongest association between ανβ6 integrins and OS in gastric cancer (HR 2.20, 95% CI 1.71–2.83) and the lowest in head and neck cancer (HR 1.21, 95% CI 0.79–1.83). There was no significant difference between early-stage and metastatic cancer, type of IHC antibodies, and analysis methods.

Conclusions

High expression of ανβ6 integrins is associated with adverse survival outcome in several tumors. Prospective studies evaluating the prognostic impact of ανβ6 integrin and its role as a therapeutic target are warranted.

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Authors and Affiliations

  1. Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, The University of Toronto, Toronto, ON, Canada

    Alexandra Desnoyers, Carlos González & Eitan Amir

  2. Experimental Therapeutics Unit, Medical Oncology Department, Health Research Institute of the Hospital Clínico San Carlos, Madrid, Spain

    Carlos González, Pedro Pérez-Segura & Alberto Ocaña

  3. Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain

    Carlos González, Atanasio Pandiella & Alberto Ocaña

  4. CIC-Universidad de Salamanca, Salamanca, Spain

    Carlos González & Atanasio Pandiella

  5. Centro Regional de Investigaciones Biomédicas, Castilla-La Mancha University (UCLM), Albacete, Spain

    Carlos González & Alberto Ocaña

Authors
  1. Alexandra Desnoyers
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  2. Carlos González
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Corresponding author

Correspondence to Alberto Ocaña.

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Conflict of interest

Dr Desnoyers, Dr González, Dr Perez-Segura, and Dr Pandiella have nothing to disclose. Dr Amir reports personal fees from Genentech/Roche, personal fees from Apobiologix, Myriad Genetics, Agendia, and Sandoz, outside the submitted work. Dr Ocaña reports grants from Daichii Sankyo, Servier, and Entrechem, outside the submitted work.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Desnoyers, A., González, C., Pérez-Segura, P. et al. Integrin ανβ6 Protein Expression and Prognosis in Solid Tumors: A Meta-Analysis. Mol Diagn Ther 24, 143–151 (2020). https://doi.org/10.1007/s40291-020-00450-1

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  • DOI: https://doi.org/10.1007/s40291-020-00450-1

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