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Abstract：
Extensive data research is helpful to find sensitive biomarkers for prognostic prediction of metastatic breast cancer. Through analyzing multiple GEO datasets, literature retrieval, and verified in GEPIA datasets, we identify BIRC5 (Baculoviral IAP repeat containing 5) and CDO1 (Cysteine dioxygenase type 1) as DEGs (differentially expressed genes) between breast tumor and normal tissue and DEGs between metastatic breast cancer and breast cancer in situ. Then, we performed a series of in silico studies on BIRC5 and CDO1 using online tools including the UALCAN, TIMER, TCGA-BRCA, LinkedOmics Kaplan-Meier Plotter, and an R script for analysis. To verify the association of 2 genes expression and patients\' clinical data, we detected BIRC5 and CDO1 mRNA in the tissue of 48 breast cancer patients. The results showed the tumor with BIRC5high CDO1low expression generally indicated patients\' shorter overall (OS) and relapse-free survival (RFS). Specifically, BIRC5 and CDO1 levels significantly affect OS or RFS in patients with Lymph node metastasis and molecular subtypes of TNBC (triple-negative breast cancer) and Luminal A. A BIRC5high tumor displayed a purer tumor purity and expressed more KIR receptors on NK cells while activating more FOXP3+CD25+ Treg cells. The CDO1low tumors infiltrated with more immunocytes leading to less tumor purity. In our verified experiment, BIRC5 mRNA level in patients with stage III and over was significantly higher than in patients with stage 0 to II, but there were no significant differences among molecular subtyping groups; TNBC tissue expressed lower CDO1 mRNA level than HER2+ and Luminal type cancer tissue. In conclusion, a BIRC5high CDO1low expression type in breast cancer tissue indicates a poorer prognosis of patients. The potential mechanism might be increased BIRC5 expression in cancer tissue is likely to accompany NK cells inhibition, activating more Treg cells, and lacking effective CD8+ T cells proliferation. Meanwhile, CDO1 level is positively related to more immunocytes infiltration.
摘要：
广泛的数据研究有助于找到敏感的生物标志物来预测转移性乳腺癌的预后。通过分析多个GEO数据集，文献检索,并在GEPIA数据集中验证，我们将BIRC5(含5个杆状病毒IAP重复序列)和CDO1(1型半胱氨酸双加氧酶)鉴定为乳腺肿瘤和正常组织之间的DEGs(差异表达基因),将DEGs鉴定为转移性乳腺癌和原位癌之间的DEGs.然后，我们使用包括UALCAN在内的在线工具对BIRC5和CDO1进行了一系列计算机模拟研究，TIMER,TCGA-BRCA,LinkedOmicsKaplan-Meier绘图仪，和用于分析的R脚本。为了验证2个基因表达与患者临床数据的相关性，我们检测了48例乳腺癌患者组织中的BIRC5和CDO1mRNA。结果表明，BIRC5高CDO1低表达的肿瘤通常表明患者的总体生存期（OS）和无复发生存期（RFS）较短。具体来说,BIRC5和CDO1水平显着影响淋巴结转移和TNBC（三阴性乳腺癌）和LuminalA分子亚型患者的OS或RFS。BIRC5高肿瘤显示出更纯的肿瘤纯度，并在NK细胞上表达更多的KIR受体，同时激活更多的FOXP3CD25Treg细胞。CDO1low肿瘤浸润的免疫细胞较多，导致肿瘤纯度较低。在我们验证的实验中，Ⅲ期及以上患者的BIRC5mRNA程度显著高于0～Ⅱ期患者，但分子亚型组之间无显著差异；TNBC组织表达CDO1mRNA水平低于HER2+和腔型癌组织。总之,乳腺癌组织中BIRC5高CDO1low表达类型提示患者预后较差。其潜在机制可能是BIRC5在癌组织中的表达增加，很可能伴随NK细胞的抑制，激活更多的Treg细胞，缺乏有效的CD8+T细胞增殖。同时,CDO1程度与更多的免疫细胞浸润呈正相干。
