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Transcobalamin I: a novel prognostic biomarker of neoadjuvant chemotherapy in locally advanced hypopharyngeal squamous cell cancers

Authors Wang Y, Yue C, Fang J, Gong L, Lian M, Wang R, Feng L, Ma H, Ma Z, Liu H

Received 24 February 2018

Accepted for publication 12 May 2018

Published 24 July 2018 Volume 2018:11 Pages 4253—4261

DOI https://doi.org/10.2147/OTT.S166514

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Ying Wang,1,2 Changli Yue,3 Jugao Fang,1,4,5 Lili Gong,2 Meng Lian,1 Ru Wang,1 Ling Feng,1 Hongzhi Ma,1 Zhihong Ma,3 Honggang Liu3

1Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Otolaryngology, Liaocheng People’s Hospital and Liaocheng Ophthalmological and Otolaryngological Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong, People’s Republic of China; 3Department of Pathology, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otorhinolaryngology, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing, People’s Republic of China

Background:
Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive head and neck squamous cell carcinoma with poor prognosis. Neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy could provide better efficacy in HPSCC treatment. Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from NACT. The aim of this study was to investigate whether transcobalamin I (TCN1) could be a novel predictive biomarker for NACT in HPSCC.
Methods: We collected biopsy specimens from 102 patients with primary locally advanced HPSCC. Messenger RNA (mRNA) and protein expression levels of TCN1 were analyzed using quantitative polymerase chain reaction and immunohistochemistry, respectively. The relationship between TCN1 expression, chemotherapy sensitivity, and clinical outcome was assessed using univariate Kaplan–Meier survival analyses and multivariate analysis with covariate adjustments. Furthermore, we knocked down TCN1 by small interfering RNA (siRNA) in HPSCC cell FaDu, tested the effects of TCN1 knockdown on cisplatin toxicity by MTT assay, and detected cisplatin-induced apoptosis by Western blotting.
Results: TCN1 expression was significantly lower in NACT-sensitive patients than non-sensitive patients at protein level (p=0.013) and mRNA level (p<0.001), indicating that low TCN1 expression predicts better NACT treatment response. Furthermore, TCN1 was an independent prognostic biomarker for both overall survival (p=0.047) and disease-free survival (p=0.05) in advanced HPSCC patients. In addition, in vitro experiments showed that genetic silencing of TCN1 using siRNA sensitized FaDu cells to cisplatin treatment with increased cell apoptosis.
Conclusion: Low expression of TCN1 might be a novel prognostic biomarker for predicting NACT sensitivity and clinical outcome in local advanced HPSCC patients.

Keywords: transcobalamin I, hypopharyngeal squamous cell carcinoma, neoadjuvant chemotherapy, prognosis biomarker

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