Guan Encui, Tian Feng, Liu Zhaoxia
Department of Gastroenterology, The Central Hospital of Linyi, Linyi, Shandong 276400, P.R. China.
Oncol Lett. 2020 Feb;19(2):1351-1367. doi: 10.3892/ol.2019.11190. Epub 2019 Dec 9.
Stomach adenocarcinoma (STAD) accounts for 95% of cases of malignant gastric cancer, which is the third leading cause of cancer-associated mortality worldwide. The pathogenesis and effective diagnosis of STAD have become popular topics for research in the previous decade. In the present study, high-throughput RNA sequencing expression profiles and clinical data from patients with STAD were obtained from The Cancer Genome Atlas database and were used as a training dataset to screen differentially expressed genes (DEGs). Prognostic DEGs were identified using univariate Cox regression analysis and were further screened by the least absolute shrinkage and selection operator regularization regression algorithm. The resulting genes were used to construct a risk score model, the validation and effectiveness evaluation of which were performed on an independent dataset downloaded from the Gene Expression Omnibus database. Stratified and functional pathway (gene set enrichment) analyses were performed on groups with different estimated prognosis. A total of 92 genes significantly associated with STAD prognosis were obtained by univariate Cox regression analysis, and 10 prognosis-associated DEGs; hemoglobin b, chromosome 4 open reading frame 48, Dickkopf WNT signaling pathway inhibitor 1, coagulation factor V, serpin family E member 1, transmembrane protein 200A, NADPH oxidase organizer 1, C-X-C motif chemokine ligand 3, mannosidase endo-α-like and tripartite motif-containing 31; were selected for the development of the risk score model. The reliability of this prognostic method was verified using a validation set, and the results of multivariate Cox analysis indicated that the risk score may serve as an independent prognostic factor. In functional DEG analysis, eight Kyoto Encyclopedia of Genes and Genomes pathways were identified to be significantly associated with STAD risk factors. Thus, the 10-gene risk score model established in the present study was regarded as credible. This risk assessment tool may help identify patients with a high risk of STAD, and the proposed prognostic mRNAs may be useful in elucidating STAD pathogenesis.
胃腺癌(STAD)占恶性胃癌病例的95%,是全球癌症相关死亡的第三大主要原因。在过去十年中,STAD的发病机制和有效诊断已成为热门研究课题。在本研究中,从癌症基因组图谱数据库中获取了STAD患者的高通量RNA测序表达谱和临床数据,并将其用作训练数据集来筛选差异表达基因(DEG)。使用单变量Cox回归分析鉴定预后DEG,并通过最小绝对收缩和选择算子正则化回归算法进一步筛选。所得基因用于构建风险评分模型,并在从基因表达综合数据库下载的独立数据集上进行验证和有效性评估。对具有不同估计预后的组进行分层和功能途径(基因集富集)分析。通过单变量Cox回归分析共获得92个与STAD预后显著相关的基因,以及10个与预后相关的DEG;血红蛋白b、4号染色体开放阅读框48、Dickkopf WNT信号通路抑制剂1、凝血因子V、丝氨酸蛋白酶抑制剂家族E成员1、跨膜蛋白200A、NADPH氧化酶组织者1、C-X-C基序趋化因子配体3、内切α-甘露糖苷酶样和含三联体基序31;被选用于开发风险评分模型。使用验证集验证了该预后方法的可靠性,多变量Cox分析结果表明风险评分可作为独立的预后因素。在功能性DEG分析中,确定了八个京都基因与基因组百科全书途径与STAD风险因素显著相关。因此,本研究建立的10基因风险评分模型被认为是可信的。这种风险评估工具可能有助于识别STAD高风险患者,并且所提出的预后mRNA可能有助于阐明STAD的发病机制。