School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 611731, China.
Sci Rep. 2023 Jan 25;13(1):1373. doi: 10.1038/s41598-023-28234-7.
Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan-Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan-Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells' expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4 T cells, B cells, CD8 T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.
胃腺癌(STAD)是一种癌症,通常在诊断时已处于晚期,临床实践中的死亡率较高。有几个因素影响 STAD 的预后,包括肿瘤微环境中免疫细胞的表达和调节。我们在这里研究了与胃癌诊断和预后相关的生物标志物,希望为未来胃癌的诊断和治疗提供思路。从癌症基因组图谱(TCGA 数据库)中获取了 STAD 和正常患者的 RNA 测序数据集。使用 R 包 DESeq2 确定和获得差异基因。使用 ESTIMATE 算法计算基质、免疫和 ESTIMATE 评分,然后使用 R 包 WGCNA 筛选模块基因。随后,取模块基因和差异基因的交集,使用 STRING 数据库进行 PPI 网络模块分析。使用 R 包 clusterProfiler、enrichplot 和 ggplot2 进行 GO 和 KEGG 富集分析。使用 Cox 回归分析筛选与生存相关的基因,最后使用 R 包 Venn Diagram 取交集获得 7 个枢纽基因。使用时间依赖性 ROC 曲线和 Kaplan-Meier 生存曲线找到了在预后中起关键作用的 SERPINE1 基因。最后,分析了 SERPINE1 在 STAD 中的表达模式、临床特征和调控机制。结果表明,与正常样本相比,STAD 样本中 SERPINE1 的表达显著增加。Cox 回归、时间依赖性 ROC 和 Kaplan-Meier 生存分析表明,SERPINE1 与 STAD 患者的不良预后显著相关。SERPINE1 的表达随着肿瘤 T、N 和 M 分类的进展而增加。此外,免疫浸润分析的结果表明,高 SERPINE1 表达组的免疫细胞表达高于低 SERPINE1 表达组,包括 CD4 T 细胞、B 细胞、CD8 T 细胞、巨噬细胞、中性粒细胞等免疫细胞。SERPINE1 与 STAD 免疫微环境中的免疫细胞密切相关,与免疫检查点 PD1 和 PD-L1 具有协同作用。总之,我们证明 SERPINE1 是 STAD 有前途的预后和诊断生物标志物,也是免疫治疗的潜在靶点。