Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma

被引：40

作者：

Nakayama, Atsuhito ^{[1
]}

Abe, Hiroyuki ^{[1
]}

Kunita, Akiko ^{[1
]}

Saito, Ruri ^{[1
]}

Kanda, Teru ^{[2
]}

Yamashita, Hiroharu ^{[3
]}

Seto, Yasuyuki ^{[3
]}

Ishikawa, Shumpei ^{[1
]}

Fukayama, Masashi ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo, Japan

[2] Tohoku Med & Pharmaceut Univ, Dept Microbiol, Sendai, Miyagi, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Gastrointestinal Surg, Tokyo, Japan

来源：

PLOS ONE | 2019年 / 14卷 / 01期

基金：

日本学术振兴会;

关键词：

EBV; DNA; CANCER;

D O I：

10.1371/journal.pone.0211358

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 EBVgenome 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.

引用

页数：13

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