Predictive biomarkers for combined chemotherapy with 5‑fluorouracil and cisplatin in oro‑ and hypopharyngeal cancers

Hasegawa,Yasuhisa; Goto,Mitsuo; Hanai,Nobuhiro; Ozawa,Taijiro; Hirakawa,Hitoshi

doi:10.3892/mco.2017.1521

Predictive biomarkers for combined chemotherapy with 5‑fluorouracil and cisplatin in oro‑ and hypopharyngeal cancers

Authors:
- Yasuhisa Hasegawa
- Mitsuo Goto
- Nobuhiro Hanai
- Taijiro Ozawa
- Hitoshi Hirakawa
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Affiliations: Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Chikusaku, Nagoya 464‑8681, Japan, Department of Maxillofacial Surgery, Aichi Gakuin University, Chikusaku, Nagoya 464‑8650, Japan, Department of Otorhinolaryngology, Toyohashi Municipal Hospital, Aotakecho, Toyohashi 441‑8570, Japan, Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of The Ryukyus, Nishiharacho, Okinawa 903‑0215, Japan
Published online on: November 29, 2017 https://doi.org/10.3892/mco.2017.1521
Pages: 378-386

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Abstract

The present study aimed to identify significant correlations between gene expression and chemotherapy response to 5‑fluorouracil (5‑FU)/cisplatin in head and neck squamous cell carcinoma (HNSCC), and to identify patients who would benefit from induction chemotherapy for both organ preservation and survival. A total of 64 patients who underwent radical treatment for HNSCC were enrolled. All patients received induction chemotherapy with 5‑FU/cisplatin and tumor responses were evaluated. Pretreatment biopsy specimens from all patients were assayed for mRNA expression of thymidylate synthase, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, tymidine phosphorylase, glutathione S‑transferase‑pi, p53, RB Transcriptional Corepressor 1, B‑cell lymphoma 2 (Bcl‑2), Bcl‑xL, E2F Transcription Factor 1, epidermal growth factor receptor, human epidermal growth factor receptor 2, phosphoinositide 3‑kinase, phosphatase and tensin homolog, vascular endothelial growth factor (VEGF), cyclooxygenase‑2, XPA, DNA Damage Recognition And Repair Factor, excision repair cross‑complementing 1 (ERCC1), multidrug resistance gene 1 (MDR1), multidrug resistance‑associated protein 1, equilibrative nucleoside transporter 1 and β‑tubulin by reverse transcription-quantitative polymerase chain reaction, and the association between the expression levels of these genes and patient response to chemotherapy was determined. The complete response (CR) group and non‑CR group for induction chemotherapy comprised 32.8 and 67.2% of patients, respectively. The 5‑year overall survival rate was significantly higher for the CR group (95%) compared with the non‑CR group (57%). According to univariate analysis, chemotherapy response was associated with T‑class and mRNA expressions of DPD, ERCC1, XPA, p53, Bcl‑2, VEGF and MDR1. Multivariate analysis identified ERCC1 expression and T‑class as significant predictors of response to chemotherapy, indicating that a DNA‑repair pathway and apoptosis pathway are pivotal mechanisms governing response to chemotherapy. The findings suggest that ERCC1 expression could be a predictive biomarker for chemotherapy response to 5‑FU/cisplatin in HNSCC. Assessing mRNA expression is a standard method for these studies, however further investigations examining polymorphisms and mutations in addition to apoptotic responses are required to determine target gene activation in HNSCC.

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