Laryngeal cancer (LC) is the second most frequent head and neck cancer in the world, roughly accounting for one-third of all head and neck cancers [
1]. It has been estimated that there will be 177,000 new cases and 95,000 LC related deaths worldwide in 2018 [
2]. Moreover, the incidence of LC has remarkably increased in China recently and is higher in males than in females (22,500 new cases in males and 2,800 new cases in females in 2015) [
3]. LC mainly originates from the epithelial tissue of the laryngeal mucosa and the majority of LC is well differentiated squamous cell carcinoma [
4]. The main clinical manifestations of LC include hoarseness, foreign body sensation of the throat, and discomfort when swallowing, sometimes with irritating cough, blood in sputum and neck bump [
5]. Many factors may lead to LC, including tobacco use, excessive alcohol consumption, virus infection and exposure to hazardous substances. Currently, surgery and/ or conservative treatment options (e.g., chemoradiotherapy and target therapy) are usually applied for LC patients based on the individual condition [
6,
7]. The prognosis of LC patients diagnosed at early stage has been improved in accordance to the development of treatment technology. However, owing to the high rates of recurrence and tendency of developing resistance to clinical therapy, the prognosis of advanced LC patients remains poor, with approximately 60% 5-year overall survival (OS) rate [
8,
9]. Although many clinical variables have been considered as major prognostic factors, comprising nodal involvement, the site and volume of the primary tumor, and stages of tumor, their invasive procedures inevitably exert negative impacts on the patients [
10]. As the development of medical laboratory techniques, several studies have identified some less invasive prognostic indicators, such as immune-related genes, inflammatory-related genes, and glycolysis-related genes [
11], also indicating prognostic values for LC patients. These indicators are proven to be reliable prognostic biomarkers, but more indicators are still needed to explore more accurate prediction for the prognosis of cancer patients.
Mutations are of benefit to evolution as a source of genetic diversity, while higher than normal rates of mutations (genomic instability) may have serious consequences for some diseases, especially various cancers. Tumor mutational burden (TMB), as a quantitative biomarker, is usually defined as the number of mutations per coding area of genomic sequence, reflecting the tumor mutation quantity. These mutations are processed into neoantigens, then they are presented to T cells, so higher TMB level may incline to harbor more neoantigens as targets for activated immune cells, which thereby increases the chances for T cell recognition and enhances anti-tumor effects [
12]. On the other hand, tumors could inhibit the reactivity of T cells via immune checkpoints, to evade immune eradication. A variety of studies have shown that compared with the patients with lower TMB levels, patients with higher TMB levels have greater response rates after immune checkpoint inhibitor therapy and experience longer survival time [
13]. Results of prior studies have suggested that high TMB level is emerging as a novel predictive biomarker of sensitivity to immunotherapy in diverse cancers [
14], while the prognostic values of TMB-related genes for LC patients have not been thoroughly explored yet. The whole exome sequencing (WES) is a golden standard for estimation of TMB in clinic, but the panel sequencing-based estimates of TMB has largely replaced WES-derived TMB due to the high prices.
In this study, we aimed to identify TMB-related genes in LC and to explore the connection between these TMB-related genes and the prognosis of LC patients. We hope to find novel predictive biomarkers to assist screening of LC patients with different prognosis.