Xia Rong, Chen Sunxiao, Chen Yan, Zhang Weiwei, Zhu Rongrong, Deng Anmei
Department of Transfusion, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Onco Targets Ther. 2015 Apr 7;8:721-6. doi: 10.2147/OTT.S81328. eCollection 2015.
The chromosomal passenger complex (CPC) acts as a key modulator for mitosis and cell cytokinesis. High levels of CPC proteins are frequently observed in multiple cancers and are correlated with more progressive malignant behaviors. The aim of the study was to evaluate whether CPC components or their combinations could be used to assess the clinical risk of patients with non-small-cell lung cancer (NSCLC).
The expression levels of four CPC proteins - aurora B kinase (AURKB), borealin, inner centromere protein (INCENP), and survivin - were evaluated using immunohistochemistry in an independent cohort of NSCLC specimens. A molecular predictor model was developed based on the combination of the four CPC proteins.
All the CPC components were overexpressed in NSCLC tumors compared with their paired adjacent normal lung tissues. Survivin overexpression was significantly correlated with late tumor stage (P=0.0166). High expressions of AURKB, INCENP, and survivin, but not borealin, were associated with shorter survival in patients with NSCLC. The constructed 4-CPC-gene model divided the cohort into two different subgroups with significantly different prognoses (hazard ratio, HR =2.8915 [95% confidence interval, CI: 1.5187-5.5052]; P=0.0013) and was retained as an independent prognostic factor in multivariate analysis (HR =2.4398 [95% CI: 1.2631-4.7127], P=0.0082). Moreover, the 4-CPC-gene model demonstrated a higher predictive ability for overall survival than each individual CPC biomarker.
Taken together, our study suggests that a molecular prognostic model based on simultaneous detection of CPC components could serve as a complement to current clinical risk stratification approaches for patients with NSCLC.
染色体乘客复合体（CPC）是有丝分裂和细胞胞质分裂的关键调节因子。在多种癌症中经常观察到高水平的CPC蛋白，且与更具侵袭性的恶性行为相关。本研究旨在评估CPC组分或其组合是否可用于评估非小细胞肺癌（NSCLC）患者的临床风险。
在一组独立的NSCLC标本中，采用免疫组织化学方法评估四种CPC蛋白——极光激酶B（AURKB）、Borealin、着丝粒内蛋白（INCENP）和生存素的表达水平。基于这四种CPC蛋白的组合建立分子预测模型。
与配对的相邻正常肺组织相比，所有CPC组分在NSCLC肿瘤中均过表达。生存素过表达与肿瘤晚期显著相关（P = 0.0166）。AURKB、INCENP和生存素的高表达而非Borealin的高表达与NSCLC患者较短的生存期相关。构建的4-CPC基因模型将队列分为两个预后显著不同的亚组（风险比，HR = 2.8915 [95%置信区间，CI：1.5187 - 5.5052]；P = 0.0013），并且在多变量分析中作为独立的预后因素保留（HR = 2.4398 [95% CI：1.2631 - 4.7127]，P = 0.0082）。此外，4-CPC基因模型对总生存期的预测能力高于每个单独的CPC生物标志物。
综上所述，我们的研究表明，基于同时检测CPC组分的分子预后模型可作为NSCLC患者当前临床风险分层方法的补充。
