title: Prognostic significance of G2/M arrest signaling pathway proteins in advanced non-small cell lung cancer patients.
abstract: The aim of the present study was to retrospectively assess the correlation between the expression levels of proteins involved in G2/M arrest signaling pathways in non-small cell lung cancer (NSCLC) tissue, as determined by immunohistochemical (IHC) methods, and the overall survival of patients with advanced stage NSCLC. IHC analysis of advanced NSCLC specimens was used to determine the expression levels of proteins involved in G2/M arrest signaling pathways, including ataxia telangiectasia mutated (ATM) kinase, ataxia telangiectasia and Rad3-related (ATR) kinase, checkpoint kinase (Chk) 1, Chk2, cell division cycle 25C (Cdc25C), total cyclin-dependent kinase 1 (Cdk1) and active Cdk1 signaling pathways, the latter of which refers to dephospho-Cdk1 (Tyr15) and phospho-Cdk1 (Thr161). Patients were enrolled continuously and followed up for ≥2 years. Univariate analysis demonstrated that the protein expression levels of dephospho-Cdk1 (P=0.015) and phospho-Cdk1 (P=0.012) exhibited prognostic significance, while the expression of the other proteins was not significantly associated with patient survival (ATM, P=0.843; ATR, P=0.245; Chk1, P=0.341; Chk2, P=0.559; Cdc25C, P=0.649; total Cdk1, P=0.093). Furthermore, the patients with tumors exhibiting low expression levels of active Cdk1 survived significantly longer than those with tumors exhibiting high active Cdk1 expression levels (P<0.05). In addition, Cox regression analysis demonstrated that the expression of active Cdk1 [odds ratio (OR), 0.624; 95% confidence ratio (CI), 0.400-0.973; P=0.038] and the pathological tumor-node-metastasis stage (OR, 0.515; 95% CI, 0.297-0.894; P=0.018) were significant independent prognostic factors for NSCLC. Therefore, the results of the present study indicated that active Cdk1 protein is an independent prognostic factor for advanced NSCLC and may validate Cdk1 as a therapeutic target for advanced NSCLC patients.
authors: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Xi'an, Shaanxi, P.R. China ; Department of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, Shaanxi, P.R. China.
authors: Jing
authors: J
authors: Wang
authors: Department of Medical Statistics, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Yuhai
authors: Y
authors: Zhang
authors: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Xi'an, Shaanxi, P.R. China.
authors: Shudi
authors: S
authors: Xu
authors: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Xi'an, Shaanxi, P.R. China.
authors: Weijie
authors: W
authors: Li
authors: Department of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, Shaanxi, P.R. China.
authors: Zhangqin
authors: Z
authors: Chen
authors: Department of Pathology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Zhe
authors: Z
authors: Wang
authors: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Xi'an, Shaanxi, P.R. China.
authors: Xinpeng
authors: X
authors: Han
authors: Department of Pathology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Yiling
authors: Y
authors: Zhao
authors: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Xi'an, Shaanxi, P.R. China.
authors: Shengqing
authors: S
authors: Li
keywords: G2/M arrest; advanced non-small cell lung cancer; molecular pathology; prognostic biomarkers