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Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma.
Nakayama, Atsuhito; Abe, Hiroyuki; Kunita, Akiko; Saito, Ruri; Kanda, Teru; Yamashita, Hiroharu; Seto, Yasuyuki; Ishikawa, Shumpei; Fukayama, Masashi.
Afiliación
  • Nakayama A; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Abe H; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Kunita A; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Saito R; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Kanda T; Department of Microbiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Yamashita H; Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Seto Y; Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Ishikawa S; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Fukayama M; Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
PLoS One ; 14(1): e0211358, 2019.
Article en En | MEDLINE | ID: mdl-30695048
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), one of four major gastric cancer types, consists of clonal growth of EBV-infected epithelial cells. However, the significance of viral loads in each tumor cell has not been evaluated. EBV-DNA is stably maintained in episomal form in the nucleus of each cancer cell. To estimate EBV copy number per genome (EBV-CN), qPCR of viral EBNA1 and host GAPDH, standardized by Namalwa DNA (one copy/genome), was applied to the formalin-fixed paraffin embedded (FFPE) surgically resected EBVaGC specimens (n = 43) and EBVaGC cell lines (SNU-719 and NCC-24). In surgical specimens, the cancer cell ratio (CCR) was determined with image analysis, and EBV-CN was obtained by adjusting qPCR value with CCR. Fluorescent in situ hybridization (FISH) was also applied to the FFPE sections using the whole EBV-genome as a probe. In surgical specimens, EBV-CN obtained by qPCR/CCR was between 1.2 and 185 copies with a median of 9.9. EBV-CN of SNU-719 and NCC-24 was 42.0 and 1.1, respectively. A linear correlation was observed with qPCR/CCR data up to 20 copies/genome (40 signals/nucleus), the limit of FISH analysis. In addition, substantial variation in the number of EBV foci was observed. Based on qPCR/CCR, high EBV-CN (>10 copies) correlated with PD-L1 expression in cancer cells (P = 0.015), but not with other pathological indicators. Furthermore, EBVaGC with high EBV-CN showed worse disease-specific survival (P = 0.041). Our findings suggest that cancer cell viral loads may contribute to expression of the immune checkpoint molecule and promotion of cancer progression in EBVaGC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Regulación hacia Arriba / Herpesvirus Humano 4 / Antígenos Nucleares del Virus de Epstein-Barr / Infecciones por Virus de Epstein-Barr / Antígeno B7-H1 Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Regulación hacia Arriba / Herpesvirus Humano 4 / Antígenos Nucleares del Virus de Epstein-Barr / Infecciones por Virus de Epstein-Barr / Antígeno B7-H1 Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos