目的 采用加权基因共表达网络分析（WGCNA）结合 RT-qPCR 实验验证探讨胃“炎-癌”转化的关键分 子生物学机制，并预测治疗胃“炎-癌”转化的潜在中药。方法 （1）通过 GEO 数据库下载基因芯片数据集 GSE2669，通过 WGCNA 判别与胃“炎-癌”转化相关的基因集模块，并绘制各相关模块的表达变化趋势；以 Reactome 数据库为背景，对各模块中的基因分别进行富集分析，探索其生物学功能；通过 STRING 网站构建胃 “炎-癌”转化相关基因集模块的蛋白互作（PPI）网络，使用最大团中心性（MCC）算法筛选各模块中评分最高的 3 个基因作为关键（Hub）基因。（2）选取 2024 年 1 月至 2024 年 6 月在广州中医药大学第一附属医院采用胃镜下 组织病理学活检确诊的慢性胃炎（CG）、肠上皮化生（IM）、胃癌（GC）患者胃黏膜组织样本各 3 例；采用 RT-qPCR 法检测胃黏膜组织中 Hub 基因的表达水平。（3）通过 Coremine Medical 数据库预测干预 Hub 基因的潜 在中药。结果 （1）得到胃“炎-癌”转化相关基因集模块包括红色、天青色、粉色、棕色和黄色模块（P＜ 0.001）。红色、天青色模块的表达量均在胃“炎-癌”转化的后期显著下调（P＜0.05，P＜0.000 1），粉色、棕 色、黄色模块均在胃“炎-癌”转化的后期显著上调（P＜0.000 1）。红色模块主要富集于特异性促炎症消退介 质（SPMs）的合成、乙醇氧化、胆汁酸和胆盐合成等生物氧化及合成通路。天青色模块主要富集于三羧酸循环、 TP53 调节代谢及呼吸链电子传递等机体代谢通路。粉色模块主要富集于中性粒细胞脱颗粒、干扰素信号、 FcγR 介导的吞噬作用等免疫调节相关信号通路。棕色模块主要富集于细胞周期、Polo 激酶等细胞增殖相关通 路。黄色模块主要富集于细胞外基质（ECM）的降解、胶原蛋白、PDGF 信号转导等上皮-间充质转化（EMT）相 关通路。（2）Hub 基因包括红色模块的 ALDH3A1、AKR1C3、AKR1C1；天青色模块的 UQCRFS1、COX5B、 NDUFV1；粉色模块的 CCR1、FCGR3B、ITGAX；棕色模块的 CCNA2、AURKB、PLK1；黄色模块的 COL1A2、 COL3A1、BGN。RT-qPCR 实验验证结果显示，ALDH3A1、AKR1C3、UQCRFS1、COX5B、NDUFV1 mRNA 表 达水平在胃“炎-癌”转化的后期显著降低（P＜0.05，P＜0.01，P＜0.001）；CCR1、FCGR3B、ITGAX、CCNA2、 AURKB、PLK1、COL1A2、COL3A1、BGN mRNA 表达水平在胃“炎-癌”转化的后期显著升高（P＜0.05，P＜ 0.01，P＜0.001）；AKR1C1 mRNA 表达水平有降低趋势，但差异无统计学意义（P＞0.05）。各模块 Hub 基因在 不同病理阶段胃黏膜组织中的表达水平与 WGCNA 各模块的表达趋势基本一致。（3）红色模块筛选得到的中药 （红参、肉苁蓉）功效主要为益气温阳；天青色模块筛选得到的中药（人参、丹参、紫草、川芎等）功效主要为行 气健脾、清热活血；粉色模块筛选得到的中药（刺五加、茯苓、猪苓等）功效主要为健脾益气、利水渗湿；棕色 模块筛选得到的中药（半枝莲、冬凌草等）功效主要为清热解毒、活血散结祛瘀；黄色模块筛选得到的中药（猫 爪草、赤芍等）功效主要为化痰散结、活血化瘀。结论 胃“炎-癌”转化涉及生物氧化及合成、机体代谢、免疫调节、细胞增殖、上皮-间充质转化等生物学过程，益气类、活血类、清热类、化痰类中药对上述生物学过 程有潜在的干预作用。

Objective To investigate the key molecular biological mechanisms underlying gastric “inflammationcancer” transformation using Weighted Gene Co-expression Network Analysis （WGCNA） combined with RT-qPCR experimental validation，and to predict potential Chinese medicines for treating this transformation. Methods （1） The gene microarray dataset GSE2669 was downloaded from the GEO database. WGCNA was used to identify gene set modules associated with gastric “inflammation-cancer” transformation，and expression trends of the relevant modules were plotted. Genes within each module were subjected to enrichment analysis using the Reactome database as background to explore their biological functions. A protein-protein interaction （PPI） network for the gene set modules related to gastric “inflammation-cancer” transformation was constructed using the STRING website. The maximal clique centrality （MCC） algorithm was used to screen the top three highest-scoring genes in each module as key （Hub） genes. （2） Three gastric mucosal tissue samples each from patients with chronic gastritis （CG），intestinal metaplasia （IM）， and gastric cancer （GC），diagnosed by histopathological biopsy under gastroscopy at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January to June 2024，were selected. The expression levels of the Hub genes in the gastric mucosal tissues were detected by RT-qPCR.（3） Potential Chinese medicines targeting the Hub genes were predicted using the Coremine Medical database. Results （1） Gene set modules related to gastric “inflammation-cancer” transformation were obtained，including the red，sky blue，pink，brown，and yellow modules （P＜0.001）. The expression levels of the red and sky blue modules were significantly downregulated in the late stage of the transformation （P＜0.05， P＜0.000 1）， while the pink， brown， and yellow modules were significantly upregulated in the late stage （P＜0.000 1）. The red module was mainly enriched in biological oxidation and synthesis pathways such as the synthesis of specialized pro-resolving mediators （SPMs），ethanol oxidation，and bile acid and bile salt synthesis. The sky blue module was mainly enriched in metabolic pathways including the tricarboxylic acid （TCA） cycle，TP53-regulated metabolism，and respiratory electron transport. The pink module was primarily enriched in immune regulation-related signaling pathways such as neutrophil degranulation，interferon signaling，and FcγRmediated phagocytosis. The brown module was mainly enriched in cell proliferation-related pathways including cell cycle and Polo-like kinase signaling. The yellow module was primarily enriched in epithelial-mesenchymal transition （EMT）-related pathways such as extracellular matrix （ECM） degradation，collagen formation，and PDGF signaling. （2） The Hub genes included ALDH3A1，AKR1C3，and AKR1C1 from the red module；UQCRFS1，COX5B，and NDUFV1 from the sky blue module；CCR1，FCGR3B，and ITGAX from the pink module；CCNA2，AURKB，and PLK1 from the brown module； and COL1A2， COL3A1， and BGN from the yellow module. RT-qPCR validation results showed that the mRNA expression levels of ALDH3A1，AKR1C3，UQCRFS1，COX5B，and NDUFV1 were significantly decreased in the late stage of the transformation （P＜0.05，P＜0.01，P＜0.001）. The mRNA expression levels of CCR1，FCGR3B，ITGAX，CCNA2，AURKB，PLK1，COL1A2，COL3A1，and BGN were significantly increased in the late stage （P＜0.05， P＜0.01， P＜0.001）. The mRNA expression level of AKR1C1 showed a decreasing trend，but the difference was not statistically significant （P＞0.05）. The expression trends of the Hub genes from each module in gastric mucosal tissues at different pathological stages were largely consistent with the expression trends of the corresponding WGCNA modules.（3） Chinese medicinals predicted from the red module （e. g.，Ginseng Radix et Rhizoma Rubra， Cistanches Herba） primarily have effects of replenishing qi and warming yang. Chinese medicinals from the sky blue module （e. g.， Ginseng Radix et Rhizoma， Salviae Miltiorrhizae Radix et Rhizoma， Arnebiae Radix，Chuanxiong Rhizoma） mainly function to promote qi flow and strengthen the spleen，clear heat and activate blood circulation. Chinese medicinals from the pink module （e.g.，Acanthopanacis Senticosi Radix et Rhizoma seu Caulis， Poria， Polyporus） primarily fortify the spleen to replenish qi， promote diuresis and drain dampness. Chinese medicinals from the brown module （e.g.，Scutellariae Barbatae Herba，Rabdosiae Rubescentis Herba） mainly clear heat and remove toxins，activate blood circulation to dissipate masses and remove blood stasis. Chinese medicinals from the yellow module （e.g.，Ranunculi Ternati Radix，Paeoniae Radix Rubra） primarily resolve phlegm to disperse nodules， activate blood circulation to resolve stasis. Conclusion Gastric “inflammation-cancer” transformation involves biological processes such as biological oxidation and synthesis，body metabolism，immune regulation，cell proliferation， and epithelial-mesenchymal transition. Chinese medicinals with effects of replenishing qi， activating blood circulation，clearing heat，and resolving phlegm have potential intervention effects on these biological processes.

R285.5；R857.3

国家重点研发计划“中医药现代化”重点专项课题（2023YFC3503602）；国家自然科学基金项目（82474404，82474408）；广东省自然 科学基金面上项目（2023A1515011019，2024A1515012532）；广东省医学科学技术研究基金项目（2024111819485438）；国家中医药传承创新中心 优势病种（慢性萎缩性胃炎）项目。