High expression levels of centromere protein A plus upregulation of the phosphatidylinositol 3‑kinase/Akt/mammalian target of rapamycin signaling pathway affect chemotherapy response and prognosis in patients with breast cancer
Songbo Zhang, Yanyan Xie, Ting Tian, Qianru Yang, Yuting Zhou, Juanjuan Qiu, Li Xu, Nan Wen, Qing Lv, Zhenggui Du
Abstract
Centromere proteins (CENPs) are involved in mitosis, and <em>CENP</em> 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 <em>CENP</em> 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 <em>CENP</em> 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. <em>CENPA, CENPE, CENPF, CENPI, CENPJ</em> and <em>CENPN</em> were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, <em>CENPA, CENPB, CENPC</em> and <em>CENPO</em> were independent factors affecting the distant relapse‑free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of <em>CENPA</em> or <em>CENPO</em> exhibited poor prognoses, whereas those with high expression levels of <em>CENPB</em> or <em>CENPC</em> 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 <em>CENPA</em> was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher <em>CENPA</em> expression levels had a worse prognosis compared with those with lower <em>CENPA</em> expression levels. Among patients with high expression levels of <em>CENPA</em>, 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 <em>CENPA</em> expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.