Liu Jiahui, Zhang Chenning, Ma Bao, Qi Jie, Zhang Xinghai, Zhao Hengli
Department of Clinical Research Center, Central Hospital, Shandong First Medical University, No. 105, Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China.
Discov Oncol. 2025 Aug 5;16(1):1473. doi: 10.1007/s12672-025-03351-z.
Colon cancer, a globally prevalent malignancy with high mortality, involves lncRNA regulation, ferroptosis pathway abnormalities, and gut microbiota dysbiosis. Ferroptosis-related gene models may aid prognostic evaluation, while microbiota metabolites modulate ferroptosis in contexts like ulcerative colitis.
Using the GEO dataset (GSE97300), we screened differentially expressed lncRNAs (e.g., AC002331.1). Competing endogenous RNA networks were predicted via miRcode and miRTarBase, followed by integration with FerrDb to establish ferroptosis regulatory relationships. GutMGene analyzed microbiota metabolite-gene interactions. A 12-gene prognostic model (e.g., HMGB1, VEGFA) was constructed using TCGA data and WEKA 3.8, validated by Kaplan-Meier analysis and ROC curves (10-fold cross-validation).
LncRNA AC002331.1 was upregulated in colon cancer and positively associated with improved OS/DFS (log-rank test, p < 0.05). Its ceRNA network regulated 29 ferroptosis-related genes. The prognostic model showed discriminative power (ROC AUC = 0.653-0.683). Model genes were co-regulated by microbiota metabolites (e.g.,succinate).
This study establishes the first lncRNA AC002331.1-centered ceRNA-ferroptosis prognostic model for colon cancer, revealing microbiota-metabolite interactions in disease progression. It provides novel mechanistic insights for therapeutic targeting.
结肠癌是一种全球流行且死亡率高的恶性肿瘤,涉及长链非编码RNA(lncRNA)调控、铁死亡途径异常和肠道微生物群失调。铁死亡相关基因模型可能有助于预后评估,而微生物群代谢产物在溃疡性结肠炎等情况下可调节铁死亡。
利用GEO数据集(GSE97300),我们筛选了差异表达的lncRNA(如AC002331.1)。通过miRcode和miRTarBase预测竞争性内源性RNA网络,随后与FerrDb整合以建立铁死亡调控关系。GutMGene分析微生物群代谢产物-基因相互作用。使用TCGA数据和WEKA 3.8构建了一个12基因的预后模型(如HMGB1、VEGFA),并通过Kaplan-Meier分析和ROC曲线(10倍交叉验证)进行验证。
lncRNA AC002331.1在结肠癌中上调,且与总生存期/无病生存期的改善呈正相关(对数秩检验,p < 0.05)。其ceRNA网络调控29个铁死亡相关基因。该预后模型显示出判别能力(ROC曲线下面积 = 0.653 - 0.683)。模型基因受微生物群代谢产物(如琥珀酸)共同调控。
本研究建立了首个以lncRNA AC002331.1为中心的结肠癌ceRNA-铁死亡预后模型,揭示了疾病进展过程中微生物群-代谢产物的相互作用。它为治疗靶点提供了新的机制见解。