title: Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients.
abstract: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Cigarette smoking is the number one risk factor which is attributed to more than four out of five cases of lung cancers. The prognostic impact of cell cycle regulation-associated tumor suppressors including p53 and p21 for NSCLC is still controversial. In the present study, we examined p53 and p21 expression using immunoblotting in tumor and adjacent non-cancerous tissues from NSCLC patients. Moreover, tissue microarrays (TMAs) including 150 specimens was used to examine p53 and p21 expression by immunohistochemical staining (IHC). The association between p53/p21 and various clinicopathological characteristics was evaluated. Kaplan-Meier overall survival was used to analyze the association between p53/p21 expression and prognosis of NSCLC patients, as well as the association of cigarette smoking with p53/p21 expression and prognosis. The results of the immunoblotting showed that expression of p53 and p21 in tumor tissues was significantly higher than that in the matched adjacent non-cancerous tissues (P<0.001 and P<0.05, respectively). The IHC results showed that 50.67% of the cases had high expression of p21; however, the percentage of patients having high expression of p53 was 31.3%. Univariate and Cox regression models were used to evaluate the factors related to prognosis with p53 and p21 expression. Multivariate analysis indicated that p53 expression was an independent prognostic factor for NSCLC (P=0.005), while p21 could not serve as an independent prognostic factor (P=0.123). In addition, smoking history was closely related to lung cancer risk (P=0.041), but could not be an independent assessment factor (P=0.740). In this study, we further demonstrated the association of p53/p21 expression and cigarette smoking. Our results suggest that cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis. The combination of p53/p21 expression and smoking history may be a useful biomarker for tumor progression and prognosis of NSCLC patients.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Xie
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Kate
authors.initials: K
authors.lastname: Huang
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Protein Quality Control and Diseases Laboratory, Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53