Prognostic value of Epstein–Barr virus DNA level for nasopharyngeal carcinoma: a meta-analysis of 8128 cases

Qu, Hongling; Huang, Yuli; Zhao, Shufen; Zhou, Yuanqing; Lv, Weibiao

doi:10.1007/s00405-019-05699-9

Cited by 29 publications

(28 citation statements)

References 35 publications

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“…This conclusion was similar to other studies [30,31]. As to pattern 2 and pattern 3, the patients of pattern 2 had a better prognosis than those of pattern 3, consistent with Qu's meta-analysis that post-treatment EBV DNA level had greater impact than pretreatment EBV DNA on clinical outcomes of NPC [19]. Moreover, the patients of pattern 4 had a worse prognosis than those of pattern 2 and 3, the possible explanation was that these patients had a higher baseline and residual tumor load [15].…”

Section: Discussionsupporting

confidence: 91%

“…Multiple reports have shown that pre-and post-treatment plasma EBV DNA are prognostic factors for NPC progression and survival [5,[14][15][16][17][18], and these ndings are also con rmed in this study. However, these previous studies mainly focused on few time points, for example, pre-treatment and 3 months posttreatment [19]. In this study, we investigated the prognostic value of plasma EBV DNA load at multiple time points during a long-time follow-up, and examined the patterns of dynamic changes in plasma EBV DNA across 4 time points (pre-treatment, 3 month, 12 month, and 24 month post-treatment).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, EBV DNA is widely considered as a reliable biomarker for early screening, clinical staging, prognosis prediction, individualized treatment and follow-up monitoring in NPC [7][8][9][10][11][12][13].While multiple studies have reported that plasma EBV DNA could be used as a predictive marker for NPC prognosis [5,[14][15][16][17][18], however, these studies only measured plasma EBV DNA load at limited time points, such as pre-treatment and 3 months post-treatment. We suggested that a long-term monitoring of dynamic changes of plasma EBV DNA could improve its prognostic value in NPC.In a meta-analysis by Qu et al [19], plasma EBV DNA was measured primarily from day 1 to 3 months post-treatment. Therefore, the prognostic value of plasma EBV DNA at other time points, such as more than 3 months post-treatment, requires further study.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

Chen

Liang

et al. 2020

Preprint

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Background: This study was performed to investigate whether long-term monitoring of dynamic changes in plasma Epstein-Barr virus (EBV) DNA could improve prognosis prediction of nasopharyngeal carcinoma (NPC).Methods: 1077 non-metastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pre-treatment and 3, 12, 24, and 36 months post-treatment. We also examined the prognostic value of dynamic changes in plasma EBV DNA at various time points.Results: Patients with plasma EBV DNA load above optimal pre- and post-treatment cut-offs had significantly worse five-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival(OS) at all time points, excluding only OS at 36 months post-treatment due to limited mortalities. Patients with persistently undetectable plasma EBV DNA at the first four time points had the best prognosis, followed by those with positive detection pre-treatment and consistently negative detection post-treatment, those with negative detection pre-treatment and positive detection at one time point post-treatment, and those with positive detection pre-treatment and at one time point post-treatment, whereas patients with positive detection at ≥2 time points post-treatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and ROC curve analysis demonstrated that the dynamic change at four time point was more valuable than any single time point for predicting disease progression, distant metastasis, locoregional relapse, and mortality.Conclusions: Dynamic changes in plasma EBV DNA pre- and post-treatment could predict the long-term survival outcome and provide accurate risk stratification in NPC.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

Chen

Liang

et al. 2020

Preprint

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“…It is well documented that the number of biomarkers might predict the prognosis of NPC, such as the EBV DNA levels, lactate dehydrogenase (LDH), SOX2, NGX6, FMNL3 and ANXA2 [4][5][6][7][8][9]. However, the molecular mechanism of NPC has not been completely established.…”

Section: Introductionmentioning

confidence: 99%

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2020

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Background Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. Methods Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. Results By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. Conclusion IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.

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“…Epstein-Barr virus(EBV)DNA concentrations correlate positively with disease stage as well as exhibit prognostic importance in NPC [22]. Many published studies have shown that EBV DNA is an important biomarker for monitoring survival for all stages of disease [23][24][25]. In stage II NPC, our previous study found that the plasma EBV-DNA level one week after radiotherapy completion could predict 3-year and 5year recurrence and metastasis rate [26], but the predictive value of pre-treatment plasma EBV-DNA level have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of ERCC1 mRNA Level and Pretreatment EBV-DNA Virus Load in Stage II Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy with Concurrent Cisplatin

Chen

Wei

et al. 2020

Preprint

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Background: The protein expression of ERCC1 in DNA repair genes was related to resistance platinum and predicting treatment outcomes in various malignant carcinoma ,the level of plasma Epstein-Barr virus（EBV）DNA concentrations is positively correlated with clinical stages of nasopharyngeal carcinoma(NPC), but the predictive value of ERCC1 mRNA and EBV-DNA level for stratified treatment with stage II NPC is unclear precisely. This study aimed to assess the predictive value of combined EBV-DNA and ERCC1 in stage II NPC patients treated with intensity-modulated radiotherapy (IMRT) with concurrent cisplatin and provide guidance for future stratified treatment.Methods: A total 78 stage II NPC patients who received IMRT and concurrent cisplatin-based chemotherapy had measurements of ERCC1 mRNA and pre-treatment EBV DNA levels by real-time PCR (RT-PCR) analysis were analyzed. Associations of ERCC1 mRNA and pre-treatment EBV DNA levels with clinical characteristics and survivals were evaluated.Results: Cut-off value of ERCC1 mRNA obtained from ROC curve was used and there were significant differences in progression-free survival (PFS) and overall survival (OS) between high expression group as compared to low expression group (P=0.021 and 0.030, respectively). Patients with pretreatment EBV-DNA<2000 copies/ml had significantly better PFS (P= 0.024) than those with pretreatment EBV-DNA≥2000 copies/ml, but there was no significant difference in OS (P= 0.062). Patients were divided into three groups by combination of ERCC1 mRNA and EBV-DNA level ERCC1 mRNA low expression/pre EBV-DNA<2000 copies/ml, ERCC1 mRNA low expression/pre EBV-DNA≥2000 copies/ml, ERCC1 mRNA high expression/pre EBV-DNA≥2000 copies/ml. In these groups, 1-year, 3-year, 5‐year OS were 100%, 100%, 100%; 100%, 94.1%, 90.9%; 100%, 85%, 72.9%, respectively (P=0.038); 1-year, 3-year, 5‐year PFS were 100%, 100%, 100%; 97.1%, 91.2%, 84.8%; 95%, 85%, 71.4%, respectively (P=0.028). Multivariate analysis showed combination of ERCC1 mRNA and EBV-DNA levels remained independent prognostic factor but not ERCC1 mRNA and EBV-DNA alone. Conclusion: Combined ERCC1 mRNA and pre EBV-DNA is a better prognostic factor in stage II NPC patients treated with concurrent chemoradiation. Patients with ERCC1 mRNA high expression/pre EBV-DNA≥2000 copies/ml should be treated with more aggressive regimen.

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Prognostic value of Epstein–Barr virus DNA level for nasopharyngeal carcinoma: a meta-analysis of 8128 cases

Cited by 29 publications

References 35 publications

Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

Predictive Value of ERCC1 mRNA Level and Pretreatment EBV-DNA Virus Load in Stage II Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy with Concurrent Cisplatin

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