Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance
Lin Mei, Xiao-Long Zhang, Rui You, You‐Ping Liu, Hongmin Cai, Lizhi Liu, Xuefei Liu, Xiong Zou, Yu‐Long Xie, Ruhai Zou, Yi-Nuan Zhang, Rui Sun, Weiyi Feng, Haiyan Wang, Guihua Tao, Haojiang Li, Wenjie Huang, Chao Zhang, Pei-Yu Huang, Jin Wang, Qi Zhao, Qi Yang, Hong-Wan Zhang, Ting Liu, Huifeng Li, Xiaobing Jiang, Jun Tang, Yangkui Gu, Tao Yu, Zhi‐Qiang Wang, Lin Feng, Tiebang Kang, Zhixiang Zuo, Ming‐Yuan Chen
Abstract
Abstract 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-γ 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.