Longitudinal analysis of genomic and immune differences between primary and metastatic nasopharyngeal carcinoma for precision oncology

Vollständiger Abstract

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Introduction Nasopharyngeal carcinoma (NPC) is a common malignancy with a high incidence in Southern China and Southeast Asia. Distant metastasis remains a major cause of poor prognosis. This study aims to explore the genomic and immune microenvironmental changes in primary and metastatic NPC through longitudinal analysis, to provide insights for guiding precision treatment strategies. Methods We analyzed tumor samples from 11 male NPC patients with distant metastasis. Paired primary and metastatic samples underwent targeted whole-exome sequencing (551 genes) and RNA sequencing (289 genes). Multiplex immunohistochemistry was performed to assess immune cell composition and immune response markers. Genomic alterations and immune features were compared between primary and metastatic tumors, and their associations with clinical outcomes were evaluated. Results Metastatic tumors exhibited distinct chromosomal changes, including frequent 1q gain, while 6p gain showed a trend toward prolonged survival. Primary tumors showed stronger immune suppression characterized by increased B-cell and Treg infiltration and elevated CTLA4 and IDO1 expression, whereas metastatic lesions displayed more active immune responses. Liver metastases presented a distinct immune landscape with lower CD8 + T-cell density compared to non-liver metastases. In locoregionally advanced NPC, high expression of oncogenic genes such as EGFR and MYC correlated with shorter disease-free survival, while elevated PANCK expression and enhanced cytotoxicity were linked to better outcomes. These results delineate the molecular and immune evolution of NPC and provide a foundation for developing precision therapeutic strategies. Conclusion This study identifies key molecular and immune features associated with NPC survival. Primary tumors show an immunosuppressive phenotype, suggesting potential benefits from combining CTLA4 or IDO1 inhibitors with PD-1 blockade. Liver metastases exhibit distinct immune features, supporting the need for site-specific precision therapies. These findings contribute to personalized management strategies in NPC, guiding treatment based on molecular and immune profiles.