In this study, data of CENPs expression and clinicopathological features of BC patients were downloaded and analyzed from the TCGA database, which aimed to discover more biological genes and molecular indexes to accurately predict the prognosis of BC. Based on the Cox regression analysis, we identified that BC patients with older age, Her2 positive, advanced T stage, advanced M stage, or low expression of CENPP were accompanied by worse OS. Next, high expression of CENPP was proved to be associated with better OS in ER + breast cancer or PR + breast cancer, whereas regardless of Her2 status, high expression of CENPP was associated with better OS. Finally, we constructed a nomogram on the basis of CENPP expression as well as other independent predictors. The 3-year and 5-year of AUCs in the training set were 0.757 and 0.797, and that of AUCs in the validation set were 0.727 and 0.71.
Cell mitosis is the process of transferring genetic information from the parent cell to the daughter cell. In the process of mitosis, CENPs not only provided energy for the separation of sister chromatids, but also served as a genomic information monitoring function. Once this process loses normal regulation or makes mistakes, it may induce the occurrence of malignant tumors[22, 23]. CENPs play a pivotal role in maintaining normal mitosis in cells. In this study, CENPP was identified as the only prognosis-related gene in CENPs for patients with BC. Some studies reported that CENPP was associated with mixed uterine carcinosarcoma and among its related pathways are mitotic metaphase, anaphase and signaling by G protein coupled receptor (GPCR)[24–26]. However, its role in BC is unknown. To our knowledge, this is the first study to investigate the prognostic value of CENPP in BC.
Hormone receptor status plays a key role in the formation and development of BC. ER and PR status as an important biological indicator of choosing treatment schemes have been widely recognized and accepted in BC patients. It has been clinically confirmed that ER + is different from ER- in predicting the clinical efficacy and survival of BC. Compared with ER- BC, the tumor differentiation of ER + BC is better, the invasiveness is lower, and the long-term survival rate is higher. According to the data of the American Registry of Cancer Research, 20% of patients with ER + breast cancer were PR-[27]. Studies have shown that ER + PR- is a more invasive subtype of ER + breast cancer[28, 29]. The overall survival and disease-free survival of ER + PR- breast cancer was lower than that of ER + PR + breast cancer. Purdie C A et al. believed that PR was an independent predictor of early breast cancer prognosis[30]. Our study found that the mRNA level of CENPP was positively associated with ER status and PR status, and higher mRNA expression of CENPP indicated better OS in BC with ER + or PR+, which suggests a close relationship between CENPP and hormone receptor pathway and the underling mechanism requires further investigation. In addition, recent studies have shown that the overexpression of Her2 did not only indicate invasiveness and poor prognosis in BC, but also predict the sensitivity of BC to systemic treatment. The result of our study showed that no matter the Her2 status was positive or negative, high expression of CENPP was associated with better OS which indicate an inconsequential association between CENPP and HER2 pathway. Collectively, these findings suggested that CENPP was an effective prognostic predictor of BC and might also be a potential target for HR + BC.
Currently, the nomogram has been developed and shown to be more accurate in predicting prognosis in some cancers than the conventional staging systems[31–33]. This study attempted to establish a prognostic nomogram of BC and to determine whether the model can accurately predict survival of patients with BC. Age, Her2 status, pathologic_T stage, pathologic_M stage and CENPP expression were identified as predictive factors for OS of BC in the multivariate Cox analysis. As we known, these variables including age, Her2 status, pathologic_T stage, pathologic_M stage were the conventional prognosis predictors in BC. This is the first study to set up a nomogram based on the CENPP expression and conventional prognosis predictors to predict OS in patients with BC. Through validated internally in the training set and externally in the validation set, the nomogram performed well in predicting survival, and its prediction was supported by the ROC curves and the calibration curves. When a patient is diagnosed with BC and has obtained the above clinicopathological results, we can predict his clinical prognosis according to her own features and CENPP expression level. If the predicted prognosis is poor, intensive treatment might be recommended in the hope of gaining a better outcome.
There’re some limitations of this study. Firstly, this was a retrospective study, all the data of this study were obtained from publicly available databases. More prospective studies are needed to further confirm our conclusions. Secondly, the demographic and clinical information provided by the TCGA database were not complete. For example, the database lacked detailed treatment records like surgery, marital status and insurance status information. Different surgical approaches, marital status and insurance status may influenced outcomes of BC patients. Despite this limitation, these researches provided more deep insights into possible molecular mechanisms of prognosis for BC.