An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma

BACKGROUND: The prognosis of nasopharyngeal carcinoma (NPC) has been recognized to improve immensely owing to radiotherapy combined with chemotherapy. However, patients with metastatic NPC have a poor prognosis. Immunotherapy has dramatically prolonged the survival of patients with NPC. Hence, further research on immune-related biomarkers is imperative to establish the prognosis of metastatic NPC. METHODS: 10 NPC RNA expression profiles were generated from patients with or without distant metastasis after chemoradiotherapy from the Fujian Cancer Hospital. The differential immune-related genes were identified and validated by immunohistochemistry analysis. The method of least absolute shrinkage and selection operator (LASSO)was used to further establish the immune-related prognostic model in an external GEO database (GSE102349, n=88). The immune microenvironment and signal pathways were evaluated in multiple dimensions at the transcriptome and single-cell levels. RESULTS: 1328 differential genes were identified, out of which 520 were upregulated and 808 were downregulated. Notably, most of the immune genes and pathways were down-regulated in the metastasis group. A prognostic immune model involving nine hub genes. Patients in low-risk group were characterized by survival advantage, hot immune phenotype and benefit from immunotherapy. Compared with immune cells, malignant cell exhibited the most active levels of risk score by ssGSEA. Accordingly, intercellular communications including LT, CD70, CD40 and SPP1, and the like, between high-risk and low-risk were explored by the R package “Cellchat”. CONCLUSION: We have constructed a model based on immunity of metastatic NPC and determined its prognostic value. The model identified the level of immune cell infiltration, cell-cell communication, along with potential immunotherapy for metastatic NPC.