Immune infiltration difference between tumor and adjacent normal regions is prognostic for gastric cancer patients.

Immune infiltration difference between tumor and adjacent normal regions is prognostic for gastric cancer patients.
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肿瘤与邻近正常区域之间的免疫浸润差异是胃癌患者的预后指标。

DOI:
10.1002/ctd2.8
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发表时间:
2022
期刊:
Clinical and translational discovery
影响因子:
--
通讯作者:
Cheng,Chao
Cheng,Chao
中科院分区:
--
文献类型:
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作者:
Zhang,Baoyi;Yao,Kevin;Cheng,Chao

文献摘要

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胃癌具有高度的异质性,无论是在肿瘤内还是在肿瘤内。为了对预后良好或对特定治疗有效率高的患者进行分层和鉴定,我们考虑了许多基因组和临床特征。然而,大多数研究从整个肿瘤的角度寻找生物标志物,如EBV感染和肿瘤浸润性淋巴细胞[1,2],从而忽略了肿瘤的异质性和空间格局。在这项研究中,我们比较了胃癌组织图像中肿瘤和邻近正常区域的淋巴细胞水平,发现浸润性淋巴细胞差异与患者的生存显著相关,这比总体浸润性和EBV状态更能预测患者的预后。我们首先使用癌症基因组图谱胃腺癌(TCGA-STAD)数据集检验了EBV感染的预后价值,其预后价值目前仍存在争议[1,3]。TCGA胃癌样本的EBV丰度是从先前的研究中获得的[4],由来自RNA-SEQ数据的每亿次读取处理的病毒支持读数(RPHM)确定。EB病毒丰度大于100RPHM者为EB病毒阳性(EBV+),其余为EB病毒阴性(EBV−)。如图1a所示,EB病毒阳性和EB病毒−样本之间的总体存活率没有显著差异。由于EBV感染是
Gastric cancer is highly heterogeneous, both inter-and intratumorally. In order to stratify and identify patients with favorable prognosis or high response rates to particular treatments, many genomic and clinical features were considered. However, most studies looked for biomarkers in view of the whole tumor, such as EBV infection and tumor infiltrating lymphocytes [1, 2], thereby ignoring tumor heterogeneity and spatial pattern. In this study, we compared lymphocyte level between tumor and adjacent normal regions in the histology images of gastric cancer, and found that the infiltrating lymphocyte difference is significantly associated with patient survival, which is more prognostic than overall infiltration and EBV status.We first examined the prognostic value of EBV infection, whose prognostic value is currently under debate [1, 3] using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) dataset. EBV abundance for TCGA gastric cancer samples was obtained from a previous study [4], determined by numbers of virus-supporting reads per hundred million reads processed (RPHM) from RNA-seq data. Samples with EBV abundance higher than 100 RPHM were considered as EBV positive (EBV+) samples, while others were considered as EBV negative (EBV−) samples. As shown in Fig. 1A, no significant overall survival difference was found between EBV+ and EBV− samples. Since EBV infection is