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Potential prognostic impact of EBV RNA-seq reads in gastric cancer: A reanalysis of The Cancer Genome Atlas cohort.
EBV RNA-seq reads 在胃癌中的潜在预后影响: 癌症基因组图谱队列的再分析。
- 影响因子：2.01
- DOI：10.1002/2211-5463.12803
- 作者列表："Sadato D","Ogawa M","Hirama C","Hishima T","Horiguchi SI","Harada Y","Shimoyama T","Itokawa M","Ohashi K","Oboki K
- 发表时间：2020-01-28
Abstract
:Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), whose prognosis remains controversial, is diagnosed by in situ hybridization of EBV-derived EBER1/2 small RNAs. In the Cancer Genome Atlas (TCGA)-Stomach Adenocarcinoma (STAD) project, the EBV molecular subtype was determined through a combination of multiple next-generation sequencing methods, but not by the gold standard in situ hybridization method. This leaves unanswered questions regarding the discordance of EBV positivity detected by different approaches and the threshold of sequencing reads. Therefore, we re-analyzed the TCGA-STAD RNA-seq dataset including 375 tumor and 32 normal samples, using our analysis pipeline. We defined a reliable threshold for EBV-derived next-generation sequencing reads by mapping them to the EBV genome with three different random arbitrary alignments. We analyzed the prognostic impact of EBV status on the histopathological subtypes of gastric cancer. EBV-positive cases identified by re-analysis comprised nearly half of the cases (49.6%) independent from infiltrating lymphocyte signatures, and showed significantly longer overall survival for adenocarcinomas of the "not otherwise specified" (NOS) type [P = 0.016 (log-rank test); HR 0.476; 95% CI 0.260-0.870, P = 0.016 (Cox univariate analysis)], but shorter overall survival for the tubular adenocarcinoma type [P = 0.005 (log-rank test); HR 3.329; 95% CI 1.406-7.885, P = 0.006 (Cox univariate analysis)]. These results demonstrate that the EBV-positivity rates were higher when determined by RNA-seq than when determined by EBER1/2 in situ hybridization. The RNA-seq-based EBV-positivity demonstrated distinct results for gastric cancer prognosis depending on the histopathological subtype, suggesting its potential to be used in clinical prognoses.
摘要
: Eb病毒 (EBV) 相关胃癌 (EBVaGC)，其预后仍存在争议，通过 EBV 衍生的 EBER1/2 小 rna 的原位杂交诊断。在癌症基因组图谱 (TCGA)-胃腺癌 (STAD) 项目中，通过多种新一代测序方法的组合确定了 EBV 分子亚型, 但不能用金标准原位杂交法。这就留下了关于不同方法检测到的 EBV 阳性的不一致性和测序读数阈值的未回答的问题。因此，我们使用我们的分析管道重新分析了包括 375 例肿瘤和 32 例正常样本的 TCGA-STAD RNA-seq 数据集。我们通过将它们映射到具有三种不同的随机任意比对的 EBV 基因组，为 EBV 衍生的下一代测序 reads 定义了一个可靠的阈值。我们分析了 EBV 状态对胃癌组织病理学亚型的预后影响。重新分析确定的 EBV 阳性病例占病例的近一半 (49.6%)，独立于浸润淋巴细胞标记, “未另行指定” (NOS) 型腺癌的总生存期显著延长 [P = 0.016 (log-rank 检验); HR 0.476; 95% CI 0.260-0.870, P = 0.016(Cox 单因素分析)]，但管状腺癌类型的总生存期较短 [P = 0.005 (log-rank 检验); HR 3.329; 95% CI 1.406-7.885, P = 0.006 (Cox 单因素分析)]。这些结果表明，RNA-seq 测定的 EBV 阳性率高于 EBER1/2 原位杂交测定的阳性率。基于 RNA-seq 的 EBV 阳性根据组织病理学亚型证明了胃癌预后的不同结果，提示其用于临床预后的潜力。
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