Head and neck squamous cell carcinoma (HNSCC), with
an overall ﬁve- year survival rate at approaching almost
50 percent, has been considered as one of the most com-
mon malignancies in recent years. Several regimens have
been put into clinical practice in HNSCC treatment,
including surgery, chemotherapy, and radiotherapy (RT).
Radiotherapy is one of the mainstay treatments of HNSCC,
and its success rate remains increasing gradually. It was
reported that nearly 75 percent patients with HNSCC beneﬁt
from radiotherapy, including both neoadjuvant and post-
operative adjuvant radiotherapies . Nevertheless, a small
proportion of patients might be radiation- resistant, and even
suffer from its toxicities, such as disorders on swallowing,
salivation, hearing, and cosmetic integrity . In some cases,
Prediction of radiotherapy response with a 5-microRNA
signature- based nomogram in head and neck squamous cell
* , Yihui Wen
*, Jingwei Zhang
, Wei Sun
, Vivian W. Y. Lui
, Yi Wei
& Weiping Wen
Department of Otolaryngology, the First Afﬁliated Hospital of Sun Yat-sen University, Guangzhou, China
Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, China
Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Afﬁliated Hospital of Sun Yat-sen University,
Faculty of Medicine, School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong SAR
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
Head and neck cancer, microRNA,
Weiping Wen, Department of
Otolaryngology, the First Afﬁliated Hospital of
Sun Yat-sen University, No.58 Zhongshan Er
Road, 510080 Guangzhou, China.
This study was supported by grants from the
Natural Science Foundation of Guangdong
Province, China (No. 2017A030310362; No.
2015A030310236) and Sun Yat-Sen
University 5010 Plan (2010004).
Received: 19 October 2017; Revised: 5
January 2018; Accepted: 8 January 2018
Cancer Medicine 2018; 7(3):726–735
*Authors contributed equally to this work as
Radiotherapy is unlikely to beneﬁt all patients with head and neck squamous cell
carcinoma (HNSCC). Therefore, novel method is warranted to predict the radio-
therapy response. Our study aimed to construct a microRNA (miRNA)- based
nomogram to predict clinical outcomes of patients with HNSCC receiving radio-
therapy. We screened out 56 differential miRNAs by analyzing 44 paired tumor
and adjacent normal samples miRNA expression proﬁles from The Cancer Genome
Atlas (TCGA). A total of 307 patients with HNSCC receiving adjuvant radiotherapy
were randomly divided into a training set (n = 154) and a validation set (n = 153).
In the training set, we combined the differential miRNA proﬁles with clinical
outcomes, and LASSO regression model was applied to establish a 5- miRNA
signature. The prediction accuracy of the 5- miRNA signature was further validated.
In addition, target genes of these miRNAs were predicted, and Gene Ontology
(GO) analysis as well as KEGG pathway analysis was executed. A 5- miRNA sig-
nature including miR- 99a, miR- 31, miR- 410, miR- 424, and miR- 495 was identiﬁed.
With a cutoff value of 1.2201 from Youden’s index, the training set was divided
into high- risk and low- risk groups, and the 5- year overall survival was signiﬁcantly
different (30% vs. 73%, HR 3.65, CI 2.46–8.16; P < 0.0001). Furthermore, our
5- miRNA signature revealed that only low- risk group would beneﬁt from radio-
therapy. Then, a nomogram combining 5- miRNA signature with clinical variables
to predict radiotherapy response was constructed. The analysis of 108 target genes
of these miRNAs revealed some potential mechanisms in HNSCC radiotherapy
response for future investigations. In conclusion, the 5- miRNA signature- based
nomogram is useful in predicting radiotherapy response in HNSCC and might
become a promising tool to optimize radiation strategies.