Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-gamma response gene expression and a higher fraction of exhausted CD8(+) T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.

Automated summary

To understand the metastasis of nasopharyngeal carcinoma, a genomic analysis was conducted on matched blood and tumor samples. Two distinct routes of metastasis were identified, one originating from lymph nodes and the other from primary tumors. The hematogenous route exhibited higher expression of IFN-gamma response genes and exhausted CD8(+) T cells. The hematogenous group showed better progression-free survival and PD-1 immunotherapy response, while the lymphatic group responded better to locoregional radiotherapy.