PloS one, 2019-01, Vol.14 (1), p.e0211358-e0211358
2019
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- Autor(en) / Beteiligte
- Titel
- Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma
- Ist Teil von
- PloS one, 2019-01, Vol.14 (1), p.e0211358-e0211358
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0211358Titel-ID: cdi_plos_journals_2172667553
- Format
- –
- Schlagworte
- Aged, Analysis, B7-H1 Antigen - genetics, Binding sites, Biology and Life Sciences, Cancer, Cancer cells, Carcinoma, Cell Line, Tumor, Cell survival, Cloning, Copy number, Copy number variations, Correlation, Cytogenetics, Deoxyribonucleic acid, Disease Progression, DNA, Epithelial cells, Epstein-Barr virus, Epstein-Barr Virus Infections - genetics, Epstein-Barr Virus Infections - virology, Epstein-Barr Virus Nuclear Antigens - genetics, Female, Fluorescence, Fluorescence in situ hybridization, Formaldehyde, Gastric cancer, Gastrointestinal surgery, Gene amplification, Gene Dosage, Gene expression, Genetic aspects, Genomes, Genomics, Glyceraldehyde-3-phosphate dehydrogenase, Herpesvirus 4, Human - genetics, Herpesvirus 4, Human - growth & development, Humans, Hybridization, Image analysis, Image processing, Image processing equipment, Immune checkpoint, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytes, Lymphoma, Male, Medical prognosis, Medicine, Medicine and Health Sciences, Middle Aged, Mutation, Nuclei (cytology), Paraffin, Paraffins, Pathology, PD-L1 protein, Prognosis, Research and Analysis Methods, Stomach cancer, Stomach Neoplasms - genetics, Stomach Neoplasms - virology, Surgery, Surgical instruments, Survival Analysis, Tumors, Up-Regulation, Viral Load, Viruses