Yang Yang, Kang Weibiao, Yuan Yu, Duan Chen, Chen Wei, Yu Changjun
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 81, Meishan Road, Shushan District, Hefei City, 230000 Anhui Province, China.
Anhui Medical University, 81, Meishan Road, Shushan District, Hefei City, 230000 Anhui Province, China.
J Oncol. 2022 Apr 25;2022:2214686. doi: 10.1155/2022/2214686. eCollection 2022.
Immunotherapy is an important treatment modality for gastric cancer, therefore, it is crucial to understand the regulators of the tumor microenvironment in gastric cancer. Numerous studies have shown that noncoding RNAs have a critical status in the tumor progression, and the influence of competing endogenous RNA (ceRNA) networks on gastric adenocarcinoma has been widely discussed over the years, but the connection between ceRNA networks and the immune microenvironment of cancer is unclear. This study was aimed at exploring how ceRNA networks influence the prognosis of patients with gastric cancer by modulating the tumor microenvironment.
The Gene Expression Omnibus was analyzed to obtain differential expression matrixes of the noncoding RNAs (circular RNAs (circRNAs), microRNAs (miRNAs)), and mRNAs. The Circular RNA Interactome web tool and TargetScan were applied to determine the miRNA binding sites of the circRNAs and miRNA target genes. The Cancer Genome Atlas provided prognostic genes for gastric cancer, and Cytoscape created the ceRNA networks. Real-time quantitative reverse transcription polymerase chain reaction and western blot assay were adopted to find out how the ceRNA network regulates the expression of the hub gene. Additionally, the TISIDB and TIMER databases were used to assess the link between the hub gene and immunotherapy, with TISIDB providing the immune genes that are coexpressed with the hub gene. Furthermore, the immune-gene signature was constructed by using Cox regression analysis. Moreover, the nomogram, which could predict the prognostic role of gastric cancer patients was created on the basis of the immune-gene signature.
In gastric cancer, the circ-0007707/miR-429/PDGFD pathway had a differential expression. The results demonstrated that the pathway could regulate the progression and immune microenvironment of gastric cancer by modulating the immune-gene signature, which included two immune genes ( and ). Moreover, the low-risk group patients had better survival.
The circ-0007707/miR-429/PDGFD pathway may play a regulatory role in the progression and prognosis of gastric cancer by interfering with the tumor microenvironment, and the PDGFD-related immune-gene signature could be considered a moderator of prognostic factor for gastric cancer and to guide immunotherapy programs.
免疫疗法是胃癌的一种重要治疗方式，因此，了解胃癌肿瘤微环境的调节因子至关重要。大量研究表明，非编码RNA在肿瘤进展中具有关键地位，多年来，竞争性内源RNA（ceRNA）网络对胃腺癌的影响已得到广泛讨论，但ceRNA网络与癌症免疫微环境之间的联系尚不清楚。本研究旨在探讨ceRNA网络如何通过调节肿瘤微环境影响胃癌患者的预后。
分析基因表达综合数据库以获得非编码RNA（环状RNA（circRNA）、微小RNA（miRNA））和信使RNA的差异表达矩阵。应用环状RNA相互作用组网络工具和TargetScan来确定circRNA的miRNA结合位点和miRNA靶基因。癌症基因组图谱提供了胃癌的预后基因，Cytoscape构建了ceRNA网络。采用实时定量逆转录聚合酶链反应和蛋白质免疫印迹分析来探究ceRNA网络如何调节枢纽基因的表达。此外，利用TISIDB和TIMER数据库评估枢纽基因与免疫疗法之间的联系，TISIDB提供与枢纽基因共表达的免疫基因。此外，通过Cox回归分析构建免疫基因特征。此外，基于免疫基因特征创建了可预测胃癌患者预后作用的值表。
在胃癌中，circ-0007707/miR-429/血小板衍生生长因子D（PDGFD）通路存在差异表达。结果表明，该通路可通过调节包括两个免疫基因（此处原文缺失具体基因名称）的免疫基因特征来调节胃癌的进展和免疫微环境。此外，低风险组患者的生存期更好。
circ-0007707/miR-429/PDGFD通路可能通过干扰肿瘤微环境在胃癌的进展和预后中发挥调节作用，并且PDGFD相关的免疫基因特征可被视为胃癌预后因素的调节因子并指导免疫治疗方案。
