Liang Jinhao, Xiang Chengjiang, Liang Yuanxiao
Department of Anorectal Surgery, Shengzhou People's Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shenzhou, China.
Department of Anorectal Surgery, Xinchang County People's Hospital, Shaoxing, Zhejiang Province, China.
Medicine (Baltimore). 2025 Jul 18;104(29):e43274. doi: 10.1097/MD.0000000000043274.
Colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) exhibit interrelated pathologies, yet the underlying mechanisms of their interaction remain largely elusive. GeGen-QinLian decoction (GQD) has shown therapeutic efficacy in both CRC and T2DM. This study aimed to elucidate the potential pharmacological mechanisms of GQD in the postoperative treatment of patients with CRC and T2DM. Transcriptomic data sets for CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis, univariate Cox regression analysis, and weighted gene coexpression network analysis were employed to identify shared genes between CRC and T2DM. Network pharmacology was used to analyze the bioactive components of GQD and their targets, identifying potential therapeutic targets for the concurrent treatment of T2DM and CRC. Enrichment analysis, immune infiltration assessment, and drug sensitivity analysis were performed, complemented by molecular docking to validate the affinity between potential targets and active components. A total of 433 shared genes between CRC and T2DM were identified, involving processes such as gene expression regulation, cell cycle control, apoptosis regulation, Wnt signaling pathway, regulation of NF-κB transcription factor activity, and inflammatory mediator regulation of transient receptor potential channels. We identified 204 bioactive components of GQD and 320 corresponding targets, of which 10 (ADRA1B [adrenergic receptor alpha 1B], CALM1 [calmodulin 1], CDKN2A [cyclin-dependent kinase inhibitor 2A], CTNNA1 [cadherin-associated protein], FCER2 [Fc fragment of IgE receptor II], GSR [glutathione reductase], GSTM1 [glutathione S-transferase mu 1], IL13 [interleukin 13], INSR [insulin receptor], and MAPK9 [mitogen-activated protein kinase 9]) were determined as potential targets for the treatment of T2DM and CRC using GQD. Enrichment analysis revealed that these targets were associated with pathways including insulin signaling pathway, cyclic guanosine monophosphate-protein kinase G signaling pathway, Ras signaling pathway, and Fc-epsilon receptor I signaling pathway. Molecular docking results demonstrated high affinity between these potential targets and active components, with the highest affinity observed between CALM1 and xambioona. This study systematically identified a set of shared genes between T2DM and CRC, along with the bioactive components and 10 potential targets of GQD for the treatment of T2DM and CRC. These findings provided a theoretical foundation for the combined therapy of T2DM and CRC.
结直肠癌（CRC）和2型糖尿病（T2DM）表现出相互关联的病理特征，但其相互作用的潜在机制仍 largely 难以捉摸。葛根芩连汤（GQD）在CRC和T2DM的治疗中均显示出疗效。本研究旨在阐明GQD在CRC合并T2DM患者术后治疗中的潜在药理机制。从癌症基因组图谱和基因表达综合数据库中检索CRC和T2DM的转录组数据集。采用差异表达分析、单变量Cox回归分析和加权基因共表达网络分析来识别CRC和T2DM之间的共享基因。利用网络药理学分析GQD的生物活性成分及其靶点，确定T2DM和CRC联合治疗的潜在治疗靶点。进行富集分析、免疫浸润评估和药物敏感性分析，并辅以分子对接来验证潜在靶点与活性成分之间的亲和力。共鉴定出CRC和T2DM之间的433个共享基因，涉及基因表达调控、细胞周期控制、凋亡调控、Wnt信号通路、NF-κB转录因子活性调控以及瞬时受体电位通道的炎症介质调控等过程。我们鉴定出GQD的204种生物活性成分和320个相应靶点，其中10个（肾上腺素能受体α1B [ADRA1B]、钙调蛋白1 [CALM1]、细胞周期蛋白依赖性激酶抑制剂2A [CDKN2A]、钙黏蛋白相关蛋白 [CTNNA1]、IgE受体II的Fc片段 [FCER2]、谷胱甘肽还原酶 [GSR]、谷胱甘肽S-转移酶μ1 [GSTM1]、白细胞介素13 [IL13]、胰岛素受体 [INSR]和丝裂原活化蛋白激酶9 [MAPK9]）被确定为使用GQD治疗T2DM和CRC的潜在靶点。富集分析表明，这些靶点与胰岛素信号通路、环磷酸鸟苷-蛋白激酶G信号通路、Ras信号通路和Fc-ε受体I信号通路等途径相关。分子对接结果表明这些潜在靶点与活性成分之间具有高亲和力，其中CALM1与xambioona之间的亲和力最高。本研究系统地鉴定出T2DM和CRC之间的一组共享基因，以及GQD治疗T2DM和CRC的生物活性成分和10个潜在靶点。这些发现为T2DM和CRC的联合治疗提供了理论基础。
