基底膜相关基因在结肠癌患者的临床预后风险评分和免疫特征  

Clinical prognostic risk score and immune profile of basement membrane-associated genes in patients with colon cancer

作　　者：陈睿鹏 臧洪婧 刘崇梅[1] 吕权新 CHEN Ruipeng;ZANG Hongjing;LIU Chongmei;LYU Quanxin(Department of Pathology,Yueyang People′s Hospital(Yueyang Hospital Affiliated to Hunan Normal University),Yueyang 414022;Department of Pathology,the Second Xiangya Hospital,Central South University;Department of Gastroenterology,the 924th Hospital of the Chinese People′s Liberation Army Joint Logistic Support Force,China)

机构地区：[1]岳阳市人民医院(湖南师范大学附属岳阳医院)病理科,湖南岳阳414022 [2]中南大学湘雅二医院病理科 [3]中国人民解放军联勤保障部队第九二四医院消化内科

出　　处：《胃肠病学和肝病学杂志》2025年第4期546-553,共8页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金青年项目(82102805);湖南省自然科学基金项目(2024JJ7594)。

摘　　要：目的探讨基底膜相关基因(basement membrane related genes,BMRGs)在结肠癌的临床预后和免疫特征。方法从文献中收集了222个BMRGs,在TCGA队列应用LASSO-Cox回归方法建立风险评分模型,并使用GSE87211队列验证。此外,构建包含BMRGs风险评分和临床因素的列线图预测结肠癌患者的生存预后。最后,评估风险评分亚组的蛋白功能富集状态、免疫浸润水平、药物敏感性分析和单细胞表达情况。结果9个BMRGs构建的风险亚组与结肠癌患者的预后高度相关(P<0.001)。其中ADAMTS4、GPC2、UNC5A、ITGA7、LAMA2、PODN是预后不佳因素,ADAMTS8、UNC5D、MMP1是预后保护因素。整合BMRGs风险评分、TNM肿瘤分期和患者年龄的列线图有助于提高预后不良患者的识别效率。蛋白功能分析显示高风险组的上调基因富集于Hedgehog信号通路并参与上皮-间充质转化;相较于高风险组,低风险组免疫细胞浸润程度更高;药物敏感性分析显示,高风险组患者对AZD7762、Wee1激酶抑制剂的敏感性较高;低风险组患者对SB505124的敏感性较高;单细胞分析显示:GPC2、ADAMTS4、PODN、LAMA2、ITGA7基因在结肠癌的肿瘤细胞中均存在高表达。结论本研究建立并验证了基于BMRGs的风险评分模型,为预测结肠癌患者的预后状态提供了一项有效的临床参考指标。Objective To investigate the clinical prognostic and immune characteristics of basement membrane-associated genes(BMRGs)in colon cancer.Methods A total of 222 BMRGs were collected from the literature.The LASSO-Cox regression method was used to establish a risk score model using the TCGA cohort,and the GSE87211 cohort was used for validation.Additionally,a Nomogram containing BMRGs risk scores and clinical factors were constructed to predict survival prognosis of colon cancer patients.Finally,protein functional enrichment status,immune infiltration levels,drug sensitivity analysis,and significant associated were evaluated for risk score subgroups.Results The risk subgroups constructed from 9 BMRGs were highly correlated with the prognosis of colon cancer patients(P<0.001).ADAMTS4,GPC2,UNC5A,ITGA7,LAMA2 and PODN were identified as poor prognostic factors,while ADAMTS8,UNC5D and MMP1 were recognized as protective prognostic factors.The integration of the BMRGs risk score,TNM tumor stage,and patient age improved the identification efficiency of patients with poor prognosis.Protein functional analysis indicated that the upregulated genes in the high-risk group were enriched in the Hedgehog signaling pathway and involved in epithelial-mesenchymal transition.Compared with the high-risk group,the infiltration degree of immune cells was higher in the low-risk group.Drug sensitivity analysis revealed that patients in the high-risk group were more sensitive to AZD7762 and Wee1 kinase inhibitors,whereas low-risk group patients showed higher sensitivity to SB505124.Single-cell analysis demonstrated that GPC2,ADAMTS4,PODN,LAMA2 and ITGA7 genes were highly expressed in colon cancer tumor cells.Conclusion This study established and validated the risk score model based on BMRGs,which provides an effective clinical reference index for predicting the prognosis of colon cancer patients.

关 键 词：基底膜相关基因 结肠癌 预后模型 列线图 生物信息学 

分 类 号：R735.3[医药卫生—肿瘤]