Predicting the radiosensitivity of HPV-negative oropharyngeal squamous cell carcinoma using miR-130b

Abstract

Background

Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma shows a higher rate of radiation resistance than HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Radioresistant HPV-negative OPSCC is associated with unfavourable outcomes, but validated prognostic biomarkers remain lacking.

Aims/Objectives

This study investigated biomarkers for radioresistant HPV-negative OPSCC.

Material and methods

The Cancer Genome Atlas included miRNA sequence and mRNA sequence data from 528 HNSCC tumours. Of these, we used gene expression data for HPV-negative head and neck squamous cell carcinoma for which data were available on the effects of radiation, and compared miRNA sequence and mRNA sequence data between radioresistant and radiosensitive groups. We subsequently estimated downstream miRNA from the results. Finally, we validated miRNAs related to the outcomes of radiotherapy in our clinical cases.

Results

Investigation of miRNA sequence revealed expression of miR-130b as the greatest difference between radiosensitive and radioresistant groups. We subsequently evaluated miR-130b expression in our clinical OPSCC cases. Values of miR-130b >5.372 (low expression), determined from receiver operating characteristic curve analyses, were associated with significantly longer progression-free survival and overall survival (p = .006, p = .04, respectively).

Conclusions and significance

Our results suggest that miR-130b has potential as a biomarker for the radiosensitivity of HPV-negative OPSCC.

Chinese abstract

背景：人类乳头瘤病毒（HPV）阴性的口咽鳞状细胞癌显示出比HPV阳性口咽鳞状细胞癌（OPSCC）更高的抗放射率。抗放射性HPV阴性OPSCC与不良预后相关, 但仍缺乏经过验证的预后生物标志物。

目的：本研究探讨了抗放射性HPV阴性OPSCC的生物标志物。

材料和方法：《癌症基因组图集》囊括了来自528例HNSCC肿瘤的miRNA序列和mRNA序列数据。其中, 我们将基因表达数据用于HPV阴性头颈部鳞状细胞癌, 对此可获得有关辐射影响的数据, 并进行了抗放射性和放射敏感性基团之间的miRNA序列和mRNA序列数据的比较。随后, 我们根据结果估算了miRNA。最后, 我们验证了我们的临床病例中与放疗结果有关的miRNA。

结果：对miRNA序列的调查显示, miR-130b表达差异在放射敏感和耐放射基团之间最大。我们随后评估了我们临床OPSCC病例中的miR-130b表达。根据受体工作特征曲线分析确定的miR-130b值> 5.372（低表达）与更长的无病情发展生存期和总生存期（分别为p¼.006, p¼.04）相关。

结论和意义：我们的结果表明, miR-130b具有潜在的HPV阴性OPSCC的放射敏感性的生物标志物作用。

Keywords:

• TCGA
• miR-130b
• p63
• head and neck cancer

Acknowledgements

We thank Dr Kazuhiko Minami and Dr Takahiro Hayashi for their continuous support, and also Ms Kozue Watanabe, and technicians in the Department of Pathology, Saitama Medical University International Medical Center, for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Hidaka Project [Grant No. 28-D-1-08].