CXCL Family-related Classification Predicts Prognosis and Response to Immunotherapy in Patients with Head and Neck Squamous Cell Carcinoma Based on TCGA and GEO Databases

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant cancer worldwide. The cysteine X cysteine (CXC) chemokine family contains 17 members, which are reportedly crucial for the growth, invasion, metastasis, and microenvironment of tumor cells. Although the precise functions of CXC ligands (CXCLs) in HNSCC are unclear, these proteins may play important roles in controlling tumor growth and forming the tumor immune environment.

Methods: We downloaded the RNA sequencing and matched clinicopathological data of 379 patients with HNSCC as the training set from The Cancer Genome Atlas and two datasets from the Gene Expression Omnibus for use as validation sets.

Results: Through consensus clustering, we identified two subtypes of HNSCC associated with the CXCL family, named cluster1 and cluster2. Patients with the cluster1 subtype showed favourable clinical outcomes, significant immune cell infiltration, and improved immune response signalling pathway modulation. We also developed a nomogram of CXCL family scores for therapeutic use and for predicting the overall survival (OS) of patients with HNSCC. Patients with lower scores showed longer OS and higher immune cell infiltration in their tissues.

Conclusions: We developed a new classification method for HNSCC using the CXCL gene family, which can be used clinically to evaluate the prognosis and response to immunotherapy in patients with HNSCC.