Peng Wen, Yang Zirong, Yan Ru, Mu Lan, Li Lan, Jin Shan, Tan Shisheng
Department of Oncology, The People's Hospital of Guizhou Province, Guiyang, China.
Institute of Life Science, eBond Pharmaceutical Technology Ltd, Chengdu, China.
Discov Oncol. 2025 May 20;16(1):837. doi: 10.1007/s12672-025-02614-z.
Colon cancer (CRC) demonstrates significant heterogeneity, and identifying effective biomarkers can advance the development of precision therapies. Emerging evidence implicates SUMOylation-regulated genes as pivotal regulators of cancer-associated pathways, yet their prognostic potential and therapeutic implications in CRC remain unexplored. A comprehensive analysis of SUMOylation-regulated gene expression, clinical and prognostic value in CRC was performed using transcriptomic data from TCGA-COAD and GEO datasets. We identified 46 differentially expressed SUMOylation-regulated genes (33 upregulated, 13 downregulated) in CRC tumors versus normal tissues. Unsupervised clustering based on 216 SUMOylation-related genes stratified CRC patients into two distinct subtypes: SUMO Cluster 1 (aggressive phenotype, poor prognosis) and SUMO Cluster 2 (favorable prognosis). Cluster 1 exhibited advanced tumor stages (N-stage, p < 0.05) and may present an immunosuppressive microenvironment marked by reduced HLA/immune checkpoint gene expression, while Cluster 2 showed enhanced anti-tumor immunity (activated dendritic cells, γδ T cells). A five-gene SUMOylation-based prognostic signature (MC1R, LRRC4C, SAGE1, GJB6, HOXC5) was developed, and patients were divided into high Riskscore and low Riskscore groups with significant survival differences (log-rank p < 0.05). The nomogram integrating risk score, age, and stage demonstrated robust predictive accuracy (C-index = 0.763, AUC = 0.728-0.785). Nomoscore-high patients exhibited resistance to AMG.706 and ABT.888, suggesting therapeutic vulnerabilities. These findings highlight SUMOylation plays a critical role in CRC heterogeneity, immune modulation, and prognosis, offering a novel biomarker system for risk stratification and personalized therapy.
结肠癌（CRC）具有显著的异质性，识别有效的生物标志物可推动精准治疗的发展。新出现的证据表明，SUMO化修饰调控的基因是癌症相关通路的关键调节因子，但其在CRC中的预后潜力和治疗意义仍未得到探索。利用来自TCGA-COAD和GEO数据集的转录组数据，对SUMO化修饰调控的基因表达、临床及预后价值进行了全面分析。我们在CRC肿瘤与正常组织中鉴定出46个差异表达的SUMO化修饰调控基因（33个上调，13个下调）。基于216个SUMO化相关基因的无监督聚类将CRC患者分为两个不同的亚型：SUMO簇1（侵袭性表型，预后不良）和SUMO簇2（预后良好）。簇1表现为肿瘤分期较晚（N分期，p<0.05），可能呈现以HLA/免疫检查点基因表达降低为特征的免疫抑制微环境，而簇2显示出增强的抗肿瘤免疫（活化的树突状细胞、γδT细胞）。开发了一种基于SUMO化修饰的五基因预后特征（MC1R、LRRC4C、SAGE1、GJB6、HOXC5），并将患者分为高风险评分组和低风险评分组，两组生存差异显著（对数秩检验p<0.05）。整合风险评分、年龄和分期的列线图显示出强大的预测准确性（C指数=0.763，AUC=0.728-0.785）。列线图评分高的患者对AMG.706和ABT.888耐药，提示存在治疗脆弱性。这些发现突出了SUMO化修饰在CRC异质性、免疫调节和预后中起关键作用，为风险分层和个性化治疗提供了一种新的生物标志物系统。
