{
  "abstract": "Background Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. The gut microbiome can influence outcomes of viral infections but the potential links among the gut microbiome, EBV infection and NPC remain unclear.Objective To characterise gut microbiome alterations in EBV-associated NPC, evaluate microbiome-based diagnostic performance (alone and in combination with EBV markers), and explore associations between microbial features, EBV DNA burden, prognosis and the tumour microenvironment.Design We conducted a large-scale shotgun metagenomic study including 516 patients with EBV-associated NPC and 263 healthy controls. Microbiome dysbiosis, functional pathways and associations with plasma EBV DNA were assessed. Species-level markers were used to build a random forest classifier for NPC diagnosis, and performance was evaluated alone and in combination with EBV-specific markers. Survival analyses were performed to identify microbial features associated with NPC-related mortality and relationships with an immune-suppressive tumour microenvironment were explored.Results NPC was characterised by gut microbiome dysbiosis, including depletion of short-chain fatty acid–producing species and reduced butanoate metabolism, which were significantly associated with plasma EBV DNA. A random forest classifier based on species-level markers distinguished NPC from controls with an area under the curve (AUC) of 0.917; performance improved to an AUC of 0.984 when combined with EBV-specific markers. Specific microbial species were associated with NPC-related mortality and prognostic microbial features were linked to an immune-suppressive tumour microenvironment.Conclusion EBV-associated NPC is associated with distinct gut microbiome and functional alterations that correlate with plasma EBV DNA. Microbial markers show strong diagnostic potential, particularly when integrated with EBV-specific markers, and prognostic microbial features may be linked to an immune-suppressive tumour microenvironment, supporting a potential role of the gut microbiome in NPC tumourigenesis.",
  "authors": [
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China",
        "Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China"
      ],
      "name": "Kaiqi Lan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Tropical Crop Breeding, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China"
      ],
      "name": "Defeng Bai"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Li Yuan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Tropical Crop Breeding, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China"
      ],
      "name": "Hao Luo"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Jing Jin"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Su-Chen Li"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Lin-Fang Wu"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Xue-Song Sun"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Sai-Lan Liu"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Qiu-Yan Chen"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Hai-Qiang Mai"
    },
    {
      "affiliations": [
        "State Key Laboratory of Tropical Crop Breeding, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China",
        "Institute of Genomics and Precision Medicine, School of Medical Technology, Gannan Medical University, Ganzhou, Jiangxi, China"
      ],
      "name": "Yong-Xin Liu"
    },
    {
      "affiliations": [
        "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, Guangdong, China",
        "Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Lin-Quan Tang"
    }
  ],
  "title": "Metagenomic identification of gut microbiome signatures for accurate diagnosis and prognostic prediction of Epstein-Barr virus-associated nasopharyngeal carcinoma",
  "uid": "d16046f8-af28-5c5b-af9d-9ad31111fcd2"
}