Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance

Mei Lin, Xiao-Long Zhang, Rui You, You-Ping Liu, Hong-Min Cai, Li-Zhi Liu, Xue-Fei Liu, Xiong Zou, Yu-Long Xie, Ru-Hai Zou, Yi-Nuan Zhang, Rui Sun, Wei-Yi Feng, Hai-Yan Wang, Gui-Hua Tao, Hao-Jiang Li, Wen-Jie Huang, Chao Zhang, Pei-Yu Huang, Jin Wang, Qi Zhao, Qi Yang, Hong-Wan Zhang, Ting Liu, Hui-Feng Li, Xiao-Bing Jiang, Jun Tang, Yang-Kui Gu, Tao Yu, Zhi-Qiang Wang, Lin Feng, Tie-Bang Kang, Zhi-Xiang Zuo () and Ming-Yuan Chen ()
Additional contact information
Mei Lin: Sun Yat-sen University Cancer Center
Xiao-Long Zhang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Rui You: Sun Yat-sen University Cancer Center
You-Ping Liu: Sun Yat-sen University Cancer Center
Hong-Min Cai: South China University of Technology
Li-Zhi Liu: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Xue-Fei Liu: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Xiong Zou: Sun Yat-sen University Cancer Center
Yu-Long Xie: Sun Yat-sen University Cancer Center
Ru-Hai Zou: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Yi-Nuan Zhang: Sun Yat-sen University Cancer Center
Rui Sun: Sun Yat-sen University Cancer Center
Wei-Yi Feng: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Hai-Yan Wang: South China Agricultural University
Gui-Hua Tao: South China University of Technology
Hao-Jiang Li: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Wen-Jie Huang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Chao Zhang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Pei-Yu Huang: Sun Yat-sen University Cancer Center
Jin Wang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Qi Zhao: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Qi Yang: Sun Yat-sen University Cancer Center
Hong-Wan Zhang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Ting Liu: Sun Yat-sen University Cancer Center
Hui-Feng Li: Sun Yat-sen University Cancer Center
Xiao-Bing Jiang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Jun Tang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Yang-Kui Gu: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Tao Yu: Sun Yat-sen University Cancer Center
Zhi-Qiang Wang: Sun Yat-sen University Cancer Center
Lin Feng: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Tie-Bang Kang: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Zhi-Xiang Zuo: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Ming-Yuan Chen: Sun Yat-sen University Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-21

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.

Date: 2023
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DOI: 10.1038/s41467-023-35995-2

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