【摘要】 目的 探讨泛素结合酶E2C(UBE2C)与乳腺癌患者预后及免疫治疗反应的关系。方法 通过生物信息学对癌症基因组图谱(TCGA)数据库中1 066例乳腺癌组织和112例癌旁正常乳腺组织中的UBE2C基因表达水平进行差异分析,通过Kaplan-Meier法分析研究UBE2C高低表达乳腺癌患者总生存期(OS)的差异。筛选UBE2C高低表达两组乳腺癌患者之间的差异基因,并进行基因本体(GO)及京都基因与基因组百科全书(KEGG)分析。通过CIBERSORT分析UBE2C与免疫细胞浸润,并利用癌症免疫组图谱(TCIA)数据库分析UBE2C与免疫治疗反应的相关性,最后通过芯片数据及免疫组化验证UBE2C在乳腺癌中的作用。结果 与癌旁正常乳腺组织相比,UBE2C在乳腺癌组织中表达明显上调,并且UBE2C高表达的乳腺癌患者OS显著缩短。UBE2C高低表达组间的差异基因主要在细胞增殖、分裂和细胞因子活性等发挥作用,且明显富集于细胞因子相关的信号通路。UBE2C高低表达组间免疫细胞浸润模式具有明显差异,UBE2C高表达组的免疫治疗效果可能更好。乳腺癌芯片与免疫组化数据均证实了UBE2C在乳腺癌中的作用。结论 UBE2C与乳腺癌患者的预后及多种免疫细胞浸润有关,可以作为预测乳腺癌免疫治疗反应的标志物。更多还原

【Abstract】 Objective To analyze the relationship of ubiquitin-conjugating enzyme E2C(UBE2C) expression with prognosis and immunotherapy response in breast cancer patients. Methods The expression status of UBE2C in 1 066 breast cancer patients and 112 adjacent tissues was obtained from the TCGA database. The correlation between UBE2C expression and the prognosis of breast cancer patients was analyzed by Kaplan-Meier curve. The differentially expressed genes between high UBE2C group and low UBE2C group of breast cancer patients were screened, and the potential function of differential genes was assessed by performing GO annotation and KEGG analyses. The relationship between UBE2C and immune infiltrates was analyzed with CIBERSORT, and the relationships between UBE2C and immunotherapy response was further analyzed with TCIA database. The role of UBE2C in breast cancer was also verified through external databases. Results Compared with adjacent tissues, the expression of UBE2C was significantly upregulated in breast cancer. The overall survival of patients with high UBE2C expression were significantly shortened. The differentially expressed genes between high UBE2C and low UBE2C group were involved in cell proliferation, division and cytokine activity, and were significantly enriched in cytokine-related signaling pathways. Immune cell infiltration mode was significantly different between patients with high and low UBE2C expression, and immunotherapy efficacy of patients with high UBE2C was better than those with low UBE2C expression. Gene chip based data and immunohistochemistry confirmed the roles of UBE2C in breast cancer. Conclusion UBE2C is associated with the prognosis of breast cancer patients and the infiltration of various immune cells, and may be used as a marker for predicting the response of immunotherapy in breast cancer patients.更多还原