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Research ArticleOriginal Article

Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients

Yongqiao He, Dawei Yang, Ting Zhou, Wenqiong Xue, Jiangbo Zhang, Fangfang Li, Fang Wang, Tongmin Wang, Ziyi Wu, Ying Liao, Meiqi Zheng, Changmi Deng, Danhua Li, Yijing Jia, Leilei Yuan, Wenli Zhang and Weihua Jia
Cancer Biology & Medicine August 2021, 18 (3) 888-899; DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0464
Yongqiao He
1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510030, China
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Dawei Yang
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
3School of Public Health, Sun Yat-sen University, Guangzhou 510030, China
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Ting Zhou
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Wenqiong Xue
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Jiangbo Zhang
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Fangfang Li
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
4Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Fang Wang
1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510030, China
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Tongmin Wang
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Ziyi Wu
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Ying Liao
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Meiqi Zheng
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
3School of Public Health, Sun Yat-sen University, Guangzhou 510030, China
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Changmi Deng
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Danhua Li
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Yijing Jia
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
3School of Public Health, Sun Yat-sen University, Guangzhou 510030, China
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Leilei Yuan
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
3School of Public Health, Sun Yat-sen University, Guangzhou 510030, China
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Wenli Zhang
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
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Weihua Jia
1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510030, China
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China
3School of Public Health, Sun Yat-sen University, Guangzhou 510030, China
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  • ORCID record for Weihua Jia
  • For correspondence: [email protected]
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    Figure 1

    Kaplan-Meier survival curves of Epstein-Barr virus DNA in peripheral blood cells for (A) overall survival, (B) progression-free survival, (C) distant metastasis-free survival, and (D) recurrence-free survival in all patients.

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    Figure 2

    Nomogram (A), including age, gender, education level, T stage, N stage, concurrent chemotherapy, body mass index, smoking status, serum lactate dehydrogenase levels, and neutrophil to lymphocyte ratio for 3-, 5-, and 10-year overall survival (OS) in patients with nasopharyngeal carcinoma. The calibration curve (B) of the nomogram for predicting OS. The Kaplan-Meier curves (C) of different risk groups in the training and validation sets according to the score system for the OS.

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    Figure 3

    A scatter plot (A) indicating the correlation between plasma Epstein-Barr virus (EBV) DNA and peripheral blood cell (PBC) EBV DNA. Grep points are the jittered points. Kaplan-Meier survival curves of overall survival. (B) plasma EBV DNA alone, (C) PBC EBV DNA alone, (D) The combination of plasma EBV DNA and PBC EBV DNA.

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    Table 1

    Multivariate Cox regression analysis of peripheral blood cell Epstein-Barr virus DNA loads in all patients

    CharacteristicsOverall survivalaProgression-free survivalaDistant metastasis-free survivalbRecurrence-free survivalb
    n./N.HR (95%CI)Pn./N.HR (95%CI)Pn./N.HR (95%CI)Pn./N.HR (95%CI)P
    ≤ 392 copies/106 globin269/752Reference–294/752Reference–115/752Reference–90/752Reference–
    392–581 copies/106 globin49/1041.50 (1.10–2.05) 0.01054/1041.50 (1.12–2.01) 0.00720/1041.31 (0.81–2.14) 0.27212/1041.05 (0.56–1.96)0.889
    581–918 copies/106 globin51/1031.52 (1.12–2.07) 0.00754/1031.46 (1.08–1.96) 0.01327/1031.76 (1.15–2.69) 0.00917/1031.61 (0.95–2.72)0.077
    > 918 copies/106 globin62/1041.85 (1.40–2.46)< 0.00164/1041.85 (1.41–2.44)< 0.00134/1042.37 (1.61–3.51)< 0.00118/1041.70 (1.01–2.87)0.047
    Ptrend< 0.001< 0.001< 0.0010.023

    n: the number of events; N: the total number of patients in each group. a: Adjusted for age, gender, smoking status, T stage, N stage, radiotherapy technology, chemotherapy (induced chemotherapy, concurrent chemotherapy, and adjuvant chemotherapy), and education levels. b: Adjusted for age, gender, smoking status, T stage, N stage, radiotherapy technology, and chemotherapy (induced chemotherapy, concurrent chemotherapy, and adjuvant chemotherapy).

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      Table 2

      Multivariate Cox regression analysis of peripheral blood cell Epstein-Barr virus DNA loads in subgroups of clinical stages

      CharacteristicsOverall survivalaProgression-free survivalaDistant metastasis-free survivalbRecurrence-free survivalb
      n./N.HR (95%CI)Pn./N.HR (95%CI)Pn./N.HR (95%CI)Pn./N.HR (95%CI)P
      Subgroup of clinical stage II
       ≤ 392 copies/106 globin27/148Reference–29/148Reference–9/148Reference–11/148Reference–
       > 392 copies/106 globin11/302.72 (1.29–5.73) 0.00814/303.38 (1.72–6.65)< 0.0017/304.96 (1.71–14.34)0.0035/303.31 (1.06–10.31)0.039
      Subgroup of Clinical stage III
       ≤ 392 copies/106 globin153/428Reference–169/428Reference–68/428Reference–56/428Reference–
       > 392 copies/106 globin76/1731.38 (1.04–1.82) 0.02580/1731.27 (0.97–1.67) 0.08136/1731.42 (0.94–2.14)0.09320/1730.97 (0.58–1.63)0.919
      Subgroup of Clinical stage IV
       ≤ 392 copies/106 globin89/176Reference–96/176Reference–38/176Reference–23/176Reference–
       > 392 copies/106 globin75/1081.92 (1.40–2.63)< 0.00178/1081.93 (1.41–2.63)< 0.00138/1082.07 (1.30–3.29)0.00222/1082.15 (1.16–3.98)0.015

      n: the number of events; N: the total number of patients in each group. a: Adjusted for age, gender, smoking status, T stage, N stage, radiotherapy technology, chemotherapy (induced chemotherapy, concurrent chemotherapy, and adjuvant chemotherapy), and education levels. b: Adjusted for age, gender, smoking status, T stage, N stage, radiotherapy technology, and chemotherapy (induced chemotherapy, concurrent chemotherapy, and adjuvant chemotherapy).

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      Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients
      Yongqiao He, Dawei Yang, Ting Zhou, Wenqiong Xue, Jiangbo Zhang, Fangfang Li, Fang Wang, Tongmin Wang, Ziyi Wu, Ying Liao, Meiqi Zheng, Changmi Deng, Danhua Li, Yijing Jia, Leilei Yuan, Wenli Zhang, Weihua Jia
      Cancer Biology & Medicine Aug 2021, 18 (3) 888-899; DOI: 10.20892/j.issn.2095-3941.2020.0464

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      Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients
      Yongqiao He, Dawei Yang, Ting Zhou, Wenqiong Xue, Jiangbo Zhang, Fangfang Li, Fang Wang, Tongmin Wang, Ziyi Wu, Ying Liao, Meiqi Zheng, Changmi Deng, Danhua Li, Yijing Jia, Leilei Yuan, Wenli Zhang, Weihua Jia
      Cancer Biology & Medicine Aug 2021, 18 (3) 888-899; DOI: 10.20892/j.issn.2095-3941.2020.0464
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      Keywords

      • nasopharyngeal carcinoma
      • Epstein-Barr virus DNA
      • prognosis
      • peripheral blood cells
      • nomogram

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