Ras相关的C3肉毒素底物2作为乳腺癌潜在预后标志物:基于免疫组织化学分析和生物信息学的研究  

RAC2 as a potential prognostic marker in breast cancer:a study based on immunohistochemical analysis and bioinformatics

作　　者：洪晨忱 俞鑫 姚峰[1] HONG Chenchen;YU Xin;YAO Feng(Department of Breast and Thyroid Surgery,Renmin Hospital of Wuhan University,Hubei Province,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院乳腺甲状腺外科,430060

出　　处：《临床外科杂志》2023年第12期1185-1190,共6页Journal of Clinical Surgery

摘　　要：目的探讨Ras相关的C3肉毒素底物2(Ras⁃related C3 botulinum toxin substrate 2,RAC2)在乳腺癌中的表达、功能和预后的价值。方法在TCGA⁃BRCA队列中研究RAC2 mRNA的表达特征,使用Kaplan⁃Meier算法分析预后价值,通过基因集富集分析研究潜在的分子功能,使用Estimate和Cibersort算法分析RAC2与免疫浸润的关系,通过maftools软件包评估RAC2与突变谱的关联,并使用RNA⁃seq软件包“pRRophetic”进行化疗药物效果预测。在验证队列中,将112例乳腺肿瘤病人肿瘤病理切片进行免疫组织化学染色,对RAC2与乳腺癌预后的关系进行Kaplan⁃Meier生存分析及Cox回归分析。结果生物信息学分析显示RAC2在雌激素受体阳性乳腺癌中表达上调,在Pam50分子亚型的乳腺癌中,其表达以正常乳腺组、三阴型组、HER2过表达组、Lu⁃minalA组、LuminalB组的顺序依次降低,RAC2高表达的乳腺癌患者有较好的总生存期和无复发生存期。验证队列的结果证实,RAC2可作为乳腺癌预后的独立预测指标。RAC2参与肿瘤细胞免疫浸润过程,其高表达主要与CCDCI68、VPS13C、AHNAK基因的突变有关。其上调增加了多柔比星、顺铂、紫杉醇、吉西他滨的药物敏感性,在代谢方面,与糖酵解及磷酸戊糖途径呈负相关,与脂肪酸氧化及谷氨酰胺代谢呈正相关。结论RAC2的高表达与乳腺癌良好的预后相关,在乳腺癌的代谢和免疫浸润中发挥作用。对RAC2相关分子机制的进一步研究可能为乳腺癌的预后判断及治疗提供新的策略。Objective To investigate the expression,function and prognostic value of Ras⁃related C3 botulinum toxin substrate 2(RAC2)in breast cancer.Methods The expression profile of RAC2 mRNA was investigated in the TCGA⁃BRCA cohort,the prognostic value was analyzed using the Kaplan⁃Meier algorithm,the potential molecular function was investigated by gene set enrichment analysis,the relationship between RAC2 and immune infiltration was analyzed by Estimate and Cibersort algorithms,and the association between Rac2 and mutation spectrum was evaluated by maftools software package.The RNA⁃seq software package“pRRophetic”was used to predict the effect of chemotherapy drugs.In the validation cohort,Immunohistochemistry(IHC)staining was performed on tumor pathological sections of patients.Kaplan⁃Meier survival analysis and cox regression analysis were used to analyze the relationship between RAC2 and the prognosis of breast cancer.Results Bioinformatics analysis showed that the expression of RAC2 was up⁃regulated in estrogen receptor(ER)positive BC.In the Pam50 molecular subtype of BC,its expression decreased in the order of normal⁃like group,triple negative group,HER2 overexpression group,Luminal A group and Luminal B group.BC patients with high RAC2 expression had better overall survival(OS)and recurrence⁃free survival(RFS).The results of the validation cohort confirmed that RAC2 can be used as an independent predictor of BC prognosis.RAC2 was involved in the process of immune infiltration of tumor cells,and its high expression was mainly related to the mutations of CCDC168,VPS13C and AHNAK genes.Its up⁃regulation increased the drug sensitivity of doxorubicin,cisplatin,paclitaxel and gemcitabine.In terms of metabolism,it was negatively correlated with glycolysis and pentose phosphate pathway(PPP),and positively correlated with fatty acid oxidation(FAO)and glutamine metabolism.Conclusion High expression of RAC2 is associated with a good prognosis of BC and plays a role in the metabolism and immune infiltrat

关 键 词：RAC2 乳腺癌 预后 生存分析 免疫 代谢 

分 类 号：R737.9[医药卫生—肿瘤]