Clinical Laboratory, General Hospital of Northern Theatre Command, Shenyang 110003, China.
Bioinformatics Department, Key laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, China.
Biosci Rep. 2020 Oct 30;40(10). doi: 10.1042/BSR20200980.
Accumulating evidence has demonstrated that tumor microenvironment (TME) plays a crucial role in stomach adenocarcinoma (STAD) development, progression, prognosis and immunotherapeutic responses. How the genes in TME interact and behave is extremely crucial for tumor investigation. In the present study, we used gene expression data of STAD available from TCGA and GEO datasets to infer tumor purity using ESTIMATE algorithms, and predicted the associations between tumor purity and clinical features and clinical outcomes. Next, we calculated the differentially expressed genes (DEGs) from the comparisons of immune and stromal scores, and postulated key biological processes and pathways that the DEGs mainly involved in. Then, we analyzed the prognostic values of DEGs in TCGA dataset, and validated the results by GEO dataset. Finally, we used CIBERSORT computational algorithm to estimate the 22 tumor infiltrating immune cells (TIICs) subsets in STAD tissues. We found that stromal and immune scores were significantly correlated with STAD subtypes, clinical stages, Helicobacter polyri infection, and stromal scores could predict the clinical outcomes in STAD patients. Moreover, we screened 307 common DEGs in TCGA and GSE51105 datasets. In the prognosis analyses, we only found OGN, JAM2, RERG, OLFML2B, and ADAMTS1 genes were significantly associated with overall survival in TCGA and GSE84437 datasets, and these genes were correlated with the fractions of T cells, B cells, macrophages, monocytes, NK cells and DC cells, respectively. Our comprehensive analyses for transcriptional data not only improved the understanding of characteristics of TME, but also provided the targets for individual therapy in STAD.
越来越多的证据表明,肿瘤微环境(TME)在胃腺癌(STAD)的发展、进展、预后和免疫治疗反应中起着关键作用。TME 中的基因如何相互作用和表现对肿瘤研究至关重要。在本研究中,我们使用来自 TCGA 和 GEO 数据集的 STAD 基因表达数据,使用 ESTIMATE 算法推断肿瘤纯度,并预测肿瘤纯度与临床特征和临床结局之间的关联。接下来,我们计算了免疫和基质评分之间差异表达基因(DEGs),并提出了 DEGs 主要涉及的关键生物学过程和途径。然后,我们分析了 TCGA 数据集 DEGs 的预后价值,并通过 GEO 数据集进行了验证。最后,我们使用 CIBERSORT 计算算法估计 STAD 组织中 22 种肿瘤浸润免疫细胞(TIICs)亚群。我们发现基质和免疫评分与 STAD 亚型、临床分期、幽门螺杆菌感染显著相关,基质评分可预测 STAD 患者的临床结局。此外,我们在 TCGA 和 GSE51105 数据集筛选出 307 个常见的 DEGs。在预后分析中,我们仅发现 OGN、JAM2、RERG、OLFML2B 和 ADAMTS1 基因在 TCGA 和 GSE84437 数据集中与总生存率显著相关,这些基因与 T 细胞、B 细胞、巨噬细胞、单核细胞、NK 细胞和 DC 细胞的分数分别相关。我们对转录组数据的综合分析不仅提高了对 TME 特征的理解,还为 STAD 的个体化治疗提供了靶标。