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Polymorphisms in the LMP1 gene in patients with gastric cancer associated with Epstein-Barr virus (Orthoherpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Lymphocryptovirus humangamma 4)

Vopr Virusol. 2026 Feb 28;71(1):62-72. doi: 10.36233/0507-4088-359.

ABSTRACT

INTRODUCTION: Epstein-Barr virus (EBV) is a widespread gamma-herpesvirus associated with a number of malignancies, including nasopharyngeal carcinoma and gastric cancer (GC/EBV+). The primary oncogenic protein of EBV is latent membrane protein 1 (LMP1). Genetic variability of the LMP1 protein affects its oncogenic activity and clinical manifestations.

OBJECTIVE: To investigate the optimal threshold value for EBV viral load, determine the correlation between high viral load and the detection of the LMP1 gene in the blood of patients with GC/EBV+, and to identify mutations in the C-terminal domains of the LMP1 gene that may affect protein function.

MATERIALS AND METHODS: Total DNA was extracted from 227 blood samples of GC patients. The LMP1 gene was amplified using nested PCR. EBV DNA viral load in blood samples was analyzed by qPCR, followed by receiver operating characteristic (ROC) analysis and interquartile range (IQR) assessment. A selection criterion for positive DNA samples (EBV+) was established based on the mean viral load and ROC threshold.

RESULTS: ROC curve analysis and descriptive statistics identified 23 EBV-positive (EBV+) DNA samples, with the following results: AUC (area under the curve) = 0.83, optimal threshold 526.92 copies/reaction, sensitivity 0.69, specificity 0.87, and mean viral load: 513.5 copies/reaction. A statistically significant association was found between detection of the LMP1 gene in the blood and viral load level (χ2 test p = 0.018; Mann-Whitney U test p < 0.0001). Additionally, synonymous and nonsynonymous mutations were identified in regions of LMP1 gene coding the C-terminal activating domains (CTAR1 and CTAR2).

CONCLUSION: The findings highlight the heterogeneous molecular nature of EBV-associated gastric cancer, including genetic mutations in the LMP1 gene.

PMID:41937671 | DOI:10.36233/0507-4088-359

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