Chen Heyan, Pu Shengyu, Yu Shibo, Liao Xiaoqin, He Jianjun, Zhang Huimin
Department of Breast Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Gland Surg. 2021 Jun;10(6):1874-1888. doi: 10.21037/gs-21-30.
In recent years, it has been found that the expression of 17 centromere proteins (CENPs) was closely related to malignant tumors, however, the role of CENPs in breast cancer (BC) has not been fully investigated. This study intends to investigate the prognostic value of CENPs in BC and establish nomogram based on expression of CENPs to predict BC patients' prognosis.
A total of 800 BC patients with complete relevant data were included from the TCGA database and were further randomly divided into training set (N=480) and validation set (N=320). Univariate and multivariate Cox regression analysis were used to screen independent factors for overall survival (OS) prediction of BC patients in the training set. Then, the nomogram was established based on these independent predictors and further validated by receiver-operating characteristic (ROC) curves and calibration plots. The GEPIA and bcGenExMiner v4.4 databases were utilized to analyze mRNA expression of candidate gene in BC patients with different clinicopathological features, respectively.
Multivariate Cox regression analysis showed that age, Her2 status, pathologic_T stage, pathologic_M stage and CENPP expression were of independent prognostic value for BC. CENPP was overexpressed in BC tissues (P<0.01) and lower expression of CENPP was associated with worse OS (P=0.005, HR =2.35; 95% CI: 1.30-4.23). We then established a nomogram based on those independent predictors, and the calibration curve demonstrated good fitness of the nomogram for OS prediction. In the training set, the AUCs of 3- and 5-year survival were 0.757 and 0.797, respectively. In the validation set, the AUCs of 3- and 5-year survival were 0.727 and 0.71, respectively.
Our study showed that CENPP was a novel prognostic factor for patients with BC, and the established nomogram could provide valuable information on prognostic prediction for patients with BC.
近年来,研究发现17种着丝粒蛋白(CENPs)的表达与恶性肿瘤密切相关,然而,CENPs在乳腺癌(BC)中的作用尚未得到充分研究。本研究旨在探讨CENPs在BC中的预后价值,并基于CENPs的表达建立列线图以预测BC患者的预后。
从TCGA数据库中纳入800例具有完整相关数据的BC患者,并进一步随机分为训练集(N = 480)和验证集(N = 320)。采用单因素和多因素Cox回归分析筛选训练集中BC患者总生存(OS)预测的独立因素。然后,基于这些独立预测因素建立列线图,并通过受试者工作特征(ROC)曲线和校准图进一步验证。利用GEPIA和bcGenExMiner v4.4数据库分别分析不同临床病理特征的BC患者中候选基因的mRNA表达。
多因素Cox回归分析显示,年龄、Her2状态、病理T分期、病理M分期和CENPP表达对BC具有独立预后价值。CENPP在BC组织中高表达(P < 0.01),CENPP低表达与较差的OS相关(P = 0.005,HR = 2.35;95% CI:1.30 - 4.23)。然后我们基于这些独立预测因素建立了列线图,校准曲线显示列线图对OS预测具有良好的拟合度。在训练集中,3年和5年生存的AUC分别为0.757和0.797。在验证集中,3年和5年生存的AUC分别为0.727和0.71。
我们的研究表明,CENPP是BC患者的一个新的预后因素,所建立的列线图可为BC患者的预后预测提供有价值的信息。