Construction and validation of a prognostic nine-gene signature associated with radiosensitivity in head and neck squamous cell carcinoma

Congxian Lu; Qi Sun; Ying Guo; Xiao Han; Mingjun Zhang; Jiahui Liu; Yaqi Wang; Yakui Mou; Yumei Li; Xicheng Song

doi:10.1016/j.ctro.2023.100686

Construction and validation of a prognostic nine-gene signature associated with radiosensitivity in head and neck squamous cell carcinoma

Clin Transl Radiat Oncol. 2023 Oct 2:43:100686. doi: 10.1016/j.ctro.2023.100686. eCollection 2023 Nov.

Authors

Congxian Lu^{1

2}, Qi Sun^{1

2}, Ying Guo^{1

2}, Xiao Han^{1

2}, Mingjun Zhang^{1

2}, Jiahui Liu^{1

2}, Yaqi Wang^{1

2}, Yakui Mou^{1

2}, Yumei Li^{1

2}, Xicheng Song^{1

2}

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai 264000, China.
² Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, China.

Abstract

Background: Radiotherapy is an effective treatment for head and neck squamous cell carcinoma (HNSCC), however how to predict the prognosis is not clear.

Methods: Here we collected 262 radiosensitivity-associated genes, screened and constructed a prognostic nine-gene risk model through univariate COX, lasso regression, stepwise regression and multivariate COX analysis for transcriptome and clinical information of HNSCC patients obtained from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases.

Results: The reliability and robustness of the risk model were verified by receiver operating characteristic (ROC) curves, risk maps, and Kaplan-Meier (KM) curves analysis. Differences in immune cell infiltration and immune-related pathway enrichment between high-risk and low-risk subgroups were determined by multiple immune infiltration analyses. Meanwhile, the mutation map and the responses to immunotherapy were also differentiated by the prognostic nine-gene signature associated with radiosensitivity. These nine genes expression in HNSCC was verified in the Human Protein Atlas (HPA) database. After that, these nine genes expression was verified to be related to radiation resistance through in-vitro cell experiments.

Conclusions: All results showed that the nine-gene signature associated with radiosensitivity is a potential prognostic indicator for HNSCC patients after radiotherapy and provides potential gene targets for enhancing the efficacy of radiotherapy.

Keywords: Head and neck squamous cell carcinoma; Immune cell infiltration; Prognostic signature; Radiosensitivity.