title: The Expression of Checkpoint and DNA Repair Genes in Head and Neck Cancer as Possible Predictive Factors.
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.
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary. rusz.orsolya@med.u-szeged.hu.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rusz
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Margit
authors.initials: M
authors.lastname: Pál
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Szilágyi
authors.affiliation: Department of Oto-Rhino-Laryngology and Head-Neck Surgery, University of Szeged, Tisza Lajos krt. 111, Szeged, H-6725, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Rovó
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Tomisa
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fábián
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Kovács
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Olga
authors.initials: O
authors.lastname: Nagy
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität, Ismaninger Straße 22, 81675, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Mózes
authors.affiliation: Department of Pathology, University of Szeged, Állomás utca 2, Szeged, H-6720, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Reisz
authors.affiliation: Department of Pathology, University of Szeged, Állomás utca 2, Szeged, H-6720, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
authors.affiliation: Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Deák
authors.affiliation: Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, H-6720, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kahán
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D000077143:Docetaxel; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D043823:Taxoids / Q000008:administration & dosage; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D043823:Taxoids; D019788:Fluorodeoxyglucose F18; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: Chemosensitivity; DNA damage response; Gene expression; Head and neck cancer; Radiosensitivity