Cancer Res Treat.  2021 Oct;53(4):991-1003. 10.4143/crt.2020.1298.

Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

• Zhang WR
• Du YY
• Guo CY
• Zhou HX
• Lin JY
• Meng XH
• Mo HY
• Luo DH

• KMID: 2521575
• DOI: http://doi.org/10.4143/crt.2020.1298

Abstract

Purpose
This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.
Materials and Methods
Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS).
Results
Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05).
Conclusion
Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Keyword

Epstein?Barr virus antibodies; Nasopharyngeal carcinoma; TNM classification; Prognosis

Figure

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  Fig. 1 Kaplan-Meier curves for 435 patients with nasopharyngeal carcinoma, stratified by IgG a tibodies against replication and transcription activator (Rta-IgG) levels (≤ 29.07 U/mL vs. > 29.07 U/mL): progression-free survival (A), overall survival (B), distant metastasis–free survival (C), and locoregional relapse–free survival (D).

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  Fig. 2 Kaplan-Meier curves for 435 patients with nasopharyngeal carcinoma stratified by EBV DNA (≤ 1,500 copies/mL vs. > 1,500 copies/mL) and Rta-IgG (≤ 29.07 U/mL vs. > 29.07 U/mL) levels: progression-free survival (A), overall survival (B), distant metastasis–free survival (C), and locoregional relapse–free survival (D). EBV, Epstein-Barr virus; HLE and HLR, high-level EBV DNA and high-level Rta-IgG group; HLE and LLR, high-level EBV DNA and low-level Rta-IgG group; LLE and HLR, low-level EBV DNA and high-level Rta-IgG group; LLE and LLR, low-level EBV DNA and low-level Rta-IgG group; Rta-IgG, IgG antibodies against replication and transcription activator.

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  Fig. 3 Kaplan-Meier curves for patients with advanced T category (T3–4) stratified by IgG antibodies against replication and transcription activator (Rta-IgG) level (≤ 29.07 vs. > 29.07 U/mL): progression-free survival (A), overall survival (B), distant metastasis–free survival (C), and locoregional relapse–free survival (D).

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  Fig. 4 Kaplan-Meier curves for patients with early N category (N0–1) stratified by IgG antibodies against replication and transcription activator (Rta-IgG) level (≤ 29.07 U/mL vs. > 29.07 U/mL): progression-free survival (A), overall survival (B), distant metastasis–free survival (C), and locoregional relapse–free survival (D).

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  Fig. 5 Kaplan-Meier curves for patients with early N category (N0–1) and low Epstein-Barr virus DNA level (≤ 1,500 copies/mL) stratified by IgG antibodies against replication and transcription activator (Rta-IgG) level (≤ 29.07 U/mL vs. > 29.07 U/mL): progression-free survival (A), overall survival (B), distant metastasis–free survival (C), and locoregional relapse–free survival (D).

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