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Clinicopathological characteristics and prognosis of Epstein-Barr virus–associated gastric cancer

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Abstract

Objective

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS).

Methods

A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis.

Results

Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%.

Conclusion

EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by Xuzhou Medical Key Talent Training Project (XWRCHT20220068); Xuzhou Medical University Hospital Development Fund Innovation Team Project (XYFC2021001), and the surface project (XYFM2021014).

Author information

Author notes

  1. Lin-lin Li, Ao-yang Yu and Mei Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China

    Lin-lin Li

  2. Graduate School of Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China

    Ao-yang Yu & Lu-yao Ma

  3. Department of Oncology, Xuzhou Cancer Hospital, Xuzhou, 221005, Jiangsu, China

    Mei Zhu

  4. Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China

    Meng-han Cao, Wen-lou Liu, Xiao-bing Qin, Chao Gao, Zheng-xiang Han & Hong-mei Wang

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  1. Lin-lin Li
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Contributions

L.L, A.Y., M.Z., and H.W. conceptualized and designed the study and drafted the initial manuscript. L.M., M.C., W.L., X.Q., and C.G. collected the data and carried out the initial analyses. Z.H. and H.W. critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Zheng-xiang Han or Hong-mei Wang.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (XYFY2021-KL063-01).

Additional information

Communicated by Zhongjie Shi.

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Li, Ll., Yu, Ay., Zhu, M. et al. Clinicopathological characteristics and prognosis of Epstein-Barr virus–associated gastric cancer. Arch Virol 169, 114 (2024). https://doi.org/10.1007/s00705-024-06033-3

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