背景:胃癌(GC)仍然是一个重要的治疗挑战,引起广泛关注。氧化苦参碱(OMT),中药复方苦参注射液(CKI)的活性成分,与化疗联合治疗GC已显示出有希望的结果。然而,OMT在GC中的治疗作用的分子机制尚未阐明。
方法:通过微阵列测序获得OMT干预后HGC-27的转录组表达数据,而GC患者的miRNA和mRNA测序数据来自TCGA数据库。从多个方面分析了OMT干预GC的机制,包括蛋白质-蛋白质相互作用(PPI),竞争性内源性RNA(ceRNA)网络,相关性和共表达分析,免疫浸润,和临床意义。
结果:通过分析关键模块,确定了五个关键的mRNA,和它们相互作用的miRNA被预测为构建一个ceRNA网络。其中,TGFBR2和hsa-miR-107与网络中的其他基因具有相关性或共表达关系。它们在大多数其他癌症中差异表达,与预后相关,具有诊断价值。TGFBR2还表现出免疫浸润现象,高表达与患者预后不良有关。hsa-miR-107的低表达与患者预后不良相关。OMT可能作用于TGFβ/Smad信号通路或通过hsa-miR-107/BTRC轴负调控WNT信号通路,从而抑制GC的发生和进展。
结论:OMT干预GC的机制多种多样,TGFBR2和hsa-miR-107可作为预后的分子生物标志物或潜在的治疗靶标。
BACKGROUND: Gastric carcinoma (GC) remains a significant therapeutic challenge, garnering widespread attention. Oxymatrine (OMT), an active component of the traditional Chinese medicine compound Kushen injection (CKI), has shown promising results in combination with chemotherapy for the treatment of GC. However, the molecular mechanisms underlying OMT\'s therapeutic effects in GC have yet to be elucidated.
METHODS: The transcriptomic expression data of HGC-27 post-OMT intervention were obtained through microarray sequencing, while the miRNA and mRNA sequencing data for GC patients were sourced from the TCGA database. The mechanism of OMT intervention in GC is analyzed in multiple aspects, including Protein-Protein Interactions (PPI), Competitive Endogenous RNA (ceRNA) networks, correlation and co-expression analyses, immune infiltration, and clinical implications.
RESULTS: By analyzing key modules, five critical mRNAs were identified, and their interacting miRNAs were predicted to construct a ceRNA network. Among these,
TGFBR2 and hsa-miR-107 have correlations or co-expression relationships with other genes in the network. They are differentially expressed in most other cancers, associated with prognosis, and have diagnostic value.
TGFBR2 also exhibits immune infiltration phenomena, and its high expression is linked to poor patient prognosis. Low expression of hsa-miR-107 is associated with poor patient prognosis. OMT may act on the TGFβ/Smad signaling pathway or negatively regulate the WNT signaling pathway through the hsa-miR-107/BTRC axis, thereby inhibiting the onset and progression of GC.
CONCLUSIONS: The mechanisms of OMT intervention in GC are diverse,
TGFBR2 and hsa-miR-107 may serve as prognostic molecular biomarkers or potential therapeutic targets.