Oncotarget

Research Papers:

Predictive single nucleotide polymorphism markers for acute oral mucositis in patients with nasopharyngeal carcinoma treated with radiotherapy

Ziyu Le, Xiaoshuang Niu, Ying Chen, Xiaomin Ou, Guoqi Zhao, Qi Liu, Wenzhi Tu, Chaosu Hu, Lin Kong and Yong Liu _

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Oncotarget. 2017; 8:63026-63037. https://doi.org/10.18632/oncotarget.18450

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Abstract

Ziyu Le1,3, Xiaoshuang Niu1,3, Ying Chen4, Xiaomin Ou1,3, Guoqi Zhao4, Qi Liu4, Wenzhi Tu4, Chaosu Hu1,3, Lin Kong1,3 and Yong Liu2,3

1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P. R. China

2Cancer Research Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P. R. China

3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China

4Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 201620, P. R. China

Correspondence to:

Yong Liu, email: [email protected]

Lin Kong, email: [email protected]

Keywords: genetic polymorphism, nasopharyngeal carcinoma, radiotherapy, oral mucositis, ZNF24

Received: March 13, 2017     Accepted: May 22, 2017     Published: June 13, 2017

ABSTRACT

The aim of this study was to investigate the association between the susceptibility of severe oral mucositis (OM) in Chinese nasopharyngeal carcinoma (NPC) patients treated with radiotherapy and single nucleotide polymorphisms (SNPs) across the whole genome. SNPs were screened in a total of 24 patients with NPC and an additional 6 were subjected to mRNA expression analysis. Patients were subdivided into CTC 0-2 (CTC toxicity grade 0, 1, and 2) and CTC 3+ (CTC toxicity grade 3 and above) groups according to their CTC (common toxicity criteria) scores. The GTEx dataset was used to performed eQTL analyses and in-vitro functional assays were performed for eQTL-associated genes. Our data identified 7 functional SNPs associated with the development of OM. We observed that rs11081899-A, located in the 5′-UTR of the ZNF24 gene, was significantly correlated with a higher risk of severe mucositis (OR = 14.631, 95% CI = 2.61-105.46, p = 1.2 × 10−4), and positively associated with ZNF24 mRNA expression (p = 4.1 × 10−6) from GTEx dataset. In addition, high ZNF24 mRNA expression was associated with severe OM in patients with NPC (p = 0.02). Further functional assays revealed that ZNF24 knockdown reduced p65 expression and suppressed TNF-α-induced NF-κB activation and pro-inflammatory cytokines release. These findings suggested that rs11081899-A may be a genetic susceptibility factor for radiation-induced OM in patients with NPC, although its value in clinical application needs to be further verified in a large cohort. Also, we suggested that downregulation of ZNF24 may attenuate the development of mucositis by suppressing NF-κB activation.


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