Abstract
Radiotherapy is unlikely to benefit all patients with head and neck squamous cell carcinoma (HNSCC). Therefore, novel method is warranted to predict the radiotherapy response. Our study aimed to construct a microRNA (miRNA)‐based nomogram to predict clinical outcomes of patients with HNSCC receiving radiotherapy. 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 signature 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 radiotherapy. 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.
Highlights
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 common malignancies in recent years
307 patients received external beam radiotherapy after surgical operation, and the radiation dose ranged from 11 Gy to 73 Gy
We evaluated the prognostic value of the 5-m iRNA signature in a total of 509 patients with HNSCC; patients in low-risk group predicted by our 5-m iRNA signature generally had better 5-year overall survival (OS) than those in high-risk group (Fig. 3A)
Summary
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 common 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 postoperative adjuvant radiotherapies [1]. 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 [2].
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