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The Expression of Checkpoint and DNA Repair Genes in Head and Neck Cancer as Possible Predictive Factors

  • Original Article
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Pathology & Oncology Research

Abstract

DNA damage response failure may influence the efficacy of DNA-damaging treatments. We determined the expression of 16 genes involved in distinct DNA damage response pathways, in association with the response to standard therapy. Twenty patients with locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric metabolic therapeutic response was determined by [18F]FDG-PET/CT. In the tumor and matched normal tissues collected before treatment, the gene expressions were examined via the quantitative real-time polymerase chain reaction (qRT-PCR). The down-regulation of TP53 was apparently associated with a poor response to iChT, its up-regulation with complete regression in 2 cases. 7 cases with down-regulated REV1 expression showed complete regression after ChRT/RT, while 1 case with REV1 overexpression was resistant to RT. The overexpression of WRN was an independent predictor of tumor relapse. Our results suggest that an altered expression of REV1 predicts sensitivity to RT, while WRN overexpression is an unfavorable prognostic factor.

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Acknowledgments

The authors are grateful for the advice of Ágnes Zvara and Ferenc Somogyvári on qRT-PCR methodology and for the advice of Krisztina Boda on statistical analysis.

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Authors and Affiliations

  1. Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary

    Orsolya Rusz, Éva Szilágyi, Zoltán Varga, Gabriella Fábián & Zsuzsanna Kahán

  2. Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary

    Margit Pál, Bernadett Tomisa, Levente Kovács, Olga Nagy & Péter Deák

  3. Department of Oto-Rhino-Laryngology and Head-Neck Surgery, University of Szeged, Tisza Lajos krt. 111, Szeged, H-6725, Hungary

    László Rovó

  4. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität, Ismaninger Straße 22, 81675, Munich, Germany

    Petra Mózes

  5. Department of Pathology, University of Szeged, Állomás utca 2, Szeged, H-6720, Hungary

    Zita Reisz & László Tiszlavicz

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  1. Orsolya Rusz
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  14. Zsuzsanna Kahán
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Corresponding author

Correspondence to Orsolya Rusz.

Additional information

The project was supported by a European Union Hungary-Romania Cross-Border Co-Operatic Programme grant (grant no. HURO/1101/173/2.2) and New Széchenyi Plan grants from the Hungarian National Development Agency (grant nos. TAMOP-4.2.2. A-11/1/KONV-2012-0035 and TAMOP-4.1.1. C-13-1-KONV)

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Rusz, O., Pál, M., Szilágyi, É. et al. The Expression of Checkpoint and DNA Repair Genes in Head and Neck Cancer as Possible Predictive Factors. Pathol. Oncol. Res. 23, 253–264 (2017). https://doi.org/10.1007/s12253-016-0088-z

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  • DOI: https://doi.org/10.1007/s12253-016-0088-z

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