Zhang Songbo, Xie Yanyan, Tian Ting, Yang Qianru, Zhou Yuting, Qiu Juanjuan, Xu Li, Wen Nan, Lv Qing, Du Zhenggui
Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2021 May;21(5):410. doi: 10.3892/ol.2021.12671. Epub 2021 Mar 22.
Centromere proteins (CENPs) are involved in mitosis, and gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. and were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, and were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of or exhibited poor prognoses, whereas those with high expression levels of or presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher expression levels had a worse prognosis compared with those with lower expression levels. Among patients with high expression levels of , the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.
着丝粒蛋白（CENPs）参与有丝分裂，其基因表达水平与乳腺癌患者的化疗反应相关。本研究旨在探讨相关基因对化疗反应及乳腺癌预后影响的作用及潜在机制。利用从基因表达综合数据库（GEO）获得的数据，采用相关性分析和Cox多因素回归分析来确定与乳腺癌患者化疗反应及生存相关的基因。运用加权基因共表达网络和相关性分析来确定与已鉴定基因共表达的基因模块，以及与病理完全缓解（PCR）和残留疾病（RD）亚组相关的基因模块的差异表达。[具体基因名称1]和[具体基因名称2]与高核分级以及低雌激素和孕激素受体表达水平相关。此外，[具体基因名称3]和[具体基因名称4]是影响乳腺癌患者远处无复发生存率（DRFS）的独立因素。[具体基因名称3]或[具体基因名称4]高表达的患者预后较差，而[具体基因名称5]或[具体基因名称6]高表达的患者预后良好。为进行数据库间验证，癌症基因组图谱（TCGA）数据库分析也显示，着丝粒蛋白A（CENPA）、着丝粒蛋白B（CENPB）和着丝粒蛋白O（CENPO）对总生存有类似影响。然而，根据多因素分析，在GEO数据库中只有[具体基因名称3]是与DRFS相关的独立危险因素。此外，在RD亚组中，[具体基因名称3]表达水平较高的患者与表达水平较低的患者相比预后更差。在[具体基因名称3]高表达的患者中，与PCR亚组相比，RD组中PI3K/Akt/mTOR通路更易被激活。在TCGA数据中也观察到相同趋势。这些结果表明，[具体基因名称3]高表达加上PI3K/Akt/mTOR信号通路的上调可能影响乳腺癌患者的DRFS。
