The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

中文翻译：

---

利用网络药理学和加权基因共表达网络进行综合分析，识别与清胰化积方治疗胰管腺癌相关的免疫相关特征。


该研究旨在通过网络药理学和加权基因共表达网络分析（WGCNA）阐明清胰化积方（QYHJ）抗胰腺癌（PC）的潜在免疫相关靶点和机制。清益活计中药材的有效成分均由TCMSP数据库鉴定。然后，使用 SwissTargetPrediction 和 STITCH 数据库预测活性成分的假定目标。 GSE32676的表达谱是从GEO数据库下载的。 WGCNA 用于识别共表达模块。此外，将推定靶标、免疫相关靶标和关键模块基因与特定疾病进行映射，以选择重叠基因（OGE）。对假定目标和 OGE 进行了功能富集分析。使用 Kaplan-Meier 绘图仪对 OGE 的总体生存 (OS) 分析进行了研究。分别在UALCAN、人类蛋白质图谱(HPA)、Oncomine、DiseaseMeth 2.0版和MEXPRESS数据库中检测OGE的相对表达和甲基化水平。进行基因集富集分析（GSEA）以进一步阐明高表达OGE的关键通路。 OS分析发现12个上调的OGE，包括CDK1、PLD1、MET、F2RL1、XDH、NEK2、TOP2A、NQO1、CCND1、PTK6、CTSE和ERBB2，可用作PC的潜在诊断指标。此外，甲基化分析表明这些OGEs的异常上调可能是由于低甲基化所致，GSEA揭示了这些基因与PC的细胞周期和增殖显着相关。 本研究发现CDK1、PLD1、MET、F2RL1、XDH、NEK2、TOP2A、NQO1、CCND1、PTK6、CTSE和ERBB2可能作为PC预后的可靠免疫相关生物标志物，可能是QYHJ的重要免疫治疗靶点。