A chromosomal passenger complex protein signature model predicts poor prognosis for non-small-cell lung cancer.

Abstract

AimThe 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).MethodsThe 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.ResultsAll 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.ConclusionTaken 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.