Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known.Methods: In this study, we calculated the immune and stromal cell scores using the “estimate” R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study.Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups.Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.

Neuregulin 1 (NRG1), as a key ligand of the epidermal growth factor receptor family, plays a crucial role in the initiation, progression, and metastasis of various solid tumors by binding to human epidermal growth factor receptor 3 (HER3) and activating downstream signaling pathways. In recent years, NRG1 gene fusions have been identified as rare oncogenic drivers in gastrointestinal tumors, with their abnormal expression in gastric and colorectal cancers closely associated with poor patient prognosis. This paper systematically reviews the biological functions and mechanisms of the NRG1/HER3 signaling axis in gastrointestinal tumors, while outlining research progress on its potential as a therapeutic target. Given the rapid development and exploratory nature of this field, this narrative review synthesizes key biological discoveries and clinical advances from current literature. It further explores the clinical prospects and challenges of therapeutic strategies targeting the NRG1/HER3 pathway, including treatment efficacy heterogeneity, complex mechanisms of drug resistance, and clinical limitations of different targeted agents. This review aims to provide a theoretical reference for subsequent research and clinical practice.