ArticleGenome biology2025
A genome-wide association study integrated with single-cell and bulk profiles uncovers susceptibility genes for nasopharyngeal carcinoma involved in tumorigenesis via regulation of T cells.
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3 citing papers in PubMed.
- Nasopharyngeal carcinoma: epidemiology, risk factors, signaling pathways, clinical features, diagnosis, and management.Molecular biomedicine · 2026Review
- Integrated Analysis of the LncRNA-Mediated ceRNA Network Associated With Prognosis in Posttreatment Recurrent Nasopharyngeal Carcinoma.Journal of cellular and molecular medicine · 2025Article
- A genome-wide association study integrated with single-cell and bulk profiles uncovers susceptibility genes for nasopharyngeal carcinoma involved in tumorigenesis via regulation of T cells.Genome biology · 2025Article
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46 authors.
Tong-Min Wang *State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Wen-Li Zhang *State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Jin-Ru Xie *State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Yong-Qiao He *State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Minzhong Tang *Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
Wen-Qiong XueState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Da-Wei YangSchool of Public Health, Sun Yat-Sen University, Guangzhou, China.
Chang-Mi DengState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Hua DiaoSchool of Public Health, Sun Yat-Sen University, Guangzhou, China.
Zhi-Ming MaiSchool of Public Health, The University of Hong Kong, Hong Kong S.A.R, China.
Ruo-Wen XiaoState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Ying LiaoState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Dan-Hua LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Yan-Xia WuState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Cheng-Tao JiangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Jiang-Bo ZhangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Xue-Yin ChenState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Yan DuState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Cao-Li TangSchool of Public Health, Sun Yat-Sen University, Guangzhou, China.
Wen-Hui JiaSchool of Public Health, Sun Yat-Sen University, Guangzhou, China.
Ting ZhouState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Xi-Zhao LiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Pei-Fen ZhangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Xiao-Hui ZhengState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Shao-Dan ZhangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Ye-Zhu HuState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Yonglin CaiWuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
Yuming ZhengWuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
Zhe ZhangDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Guangfu JinDepartment of Epidemiology, International Joint Research Center On Environment and Human Health, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
Wen ChenSchool of Public Health, Sun Yat-Sen University, Guangzhou, China.
Hai-Qiang MaiDepartment of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Ying SunDepartment of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Zhibin HuDepartment of Epidemiology, International Joint Research Center On Environment and Human Health, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
Jianjun LiuHuman Genetics, Agency for Science, Technology and Research (A*STAR), Genome Institute of Singapore, Singapore, Singapore.
Xin-Yuan GuanState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Fan BaiBiomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China.
Jinxin BeiState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Jun MaDepartment of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Musheng ZengState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Maria Li LungDepartment of Clinical Oncology, School of Clinical Medicine, University of Hong Kong , Hong Kong S.A.R, China.
Hans-Olov AdamiClinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
Weimin YeDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Tai-Hing LamSchool of Public Health, The University of Hong Kong, Hong Kong S.A.R, China.
Hongbing ShenDepartment of Epidemiology, International Joint Research Center On Environment and Human Health, Center for Global Health, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
Wei-Hua JiaState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China. jiawh@sysucc.org.cn.
Funding
Cancer Innovative Research Program of Sun Yat-sen University Cancer Center CIRP-SYSUCC-0017Noncommunicable Chronic Diseases-National Science and Technology Major Project 2023ZD0501000the Fundamental Research Funds for the Central Universities, Sun Yat-sen University 24qnpy292the Fundamental Research Funds for the Central Universities, Sun Yat-sen University 24ykqb002the National Natural Science Foundation of China 82273705the National Natural Science Foundation of China 82373656the National Natural Science Foundation of China 82404339the National Natural Science Foundation of China 82473703the Science and Technology Planning Project of Guangzhou, China 2024A04J00693the Science and Technology Planning Project of Guangzhou, China 2024A04J4560the Young Talents Program of Sun Yat-sen University Cancer Center YTP-SYSUCC-0076the Young Talents Program of Sun Yat-sen University Cancer Center YTP-SYSUCC-0081the Young Talent Support Project of Guangzhou Association for Science and Technology QT2024-030Young Science and Technology Talent Support Program of Guangdong Precision Medicine Application Association YSTTGDPMAA202502
Abstract
backgroundNasopharyngeal carcinoma is an aggressive malignancy originating from the nasopharyngeal mucosa and associated with genetic factors. Many nasopharyngeal carcinoma susceptibility loci have been identified by genome-wide association studies (GWASs), but their underlying functional insights are largely unexplained.
resultsA meta-GWAS including 5073 nasopharyngeal carcinoma patients and 5860 controls from nasopharyngeal carcinoma endemic areas identifies a total of 863 significant SNPs, including SNPs at a novel locus 3p24.1 (rs56365817; nearby genes: CMC1/EOMES). By integrating the GWAS signals with single-cell and bulk profiles, we find nasopharyngeal carcinoma susceptibility robustly associated with T cells in different methods and datasets. In nasopharyngeal carcinoma-associated cell type, we identify 234 putative susceptibility genes (81.62% of them novel), mainly enriched in immune-related biological processes. Five putative causal genes are prioritized. We perform in-depth bioinformatic analysis and functional experiments for EOMES, finding that the nasopharyngeal carcinoma-risk alleles of four functional SNPs upregulate EOMES expression by promoting the activity of regulatory elements in T cells, and EOMES participates in nasopharyngeal carcinoma tumorigenesis via regulation of CD8
conclusionsThis study uncovers novel nasopharyngeal carcinoma susceptibility genes and their functional cell types, which improves the understanding of nasopharyngeal carcinoma genetic etiology.
Indexed as
CarcinogenesisGenetic Predisposition to DiseaseNasopharyngeal CarcinomaNasopharyngeal NeoplasmsT-LymphocytesGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansPolymorphism, Single NucleotideSingle-Cell AnalysisT-Box Domain ProteinsEOMES protein, humanT-Box Domain Proteins
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