title: Expression of p16 in non-small cell lung cancer and its prognostic significance: a meta-analysis of published literatures.
abstract: The prognostic value of p16 for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. we performed a meta-analysis of the literatures in order to clarify its impact. Published studies in English were identified using an electronic search in order to aggregate the available survival results. To be eligible, a study had to have dealt with p16 protein assessment in NSCLC patients on the primary site and have reported survival data according to p16 expression. Twenty trials, comprising 1995 patients, provided sufficient information for the meta-analysis. Seventeen assessed any non-small cell lung cancer subtype, three assessed adenocarcinoma only. Eight identified high p16 expression as a favourable prognostic factor and one linked it with poor prognosis, Eleven trials were not significant. The overall combined hazard ratio (HR) calculated using a random-effects model suggested that high p16 expression has a favourable impact on survival in all NSCLC [0.69, 95% CI: 0.59-0.81]; The studies were categorized according to histology, disease stage and laboratory technique. The aggregated survival data showed a poor survival prognosis in squamous cell cancer with lower p16 expression [0.34, 95% CI: 0.13-0.91]. The adenocarcinoma subgroup had an HR of 0.91 [95% CI 0.76-1.10] without statistical significance. In early stage NSCLC (I-II), the aggregated HR was 0.42 [95% CI: 0.28-0.63], showing a worse survival for NSCLC with abnormal p16 expression; Results were significant with the HR of 0.61 [95% CI: 0.45-0.82] for five studies detecting p16 by immunohistochemistry with antibody clone G175-405. In conclusion, our meta-analysis shows that the p16 expression status is an independent prognostic factor in NSCLC, and this tendency is also found in the subgroups of squamous cell lung cancer and early stage NSCLC (I-II), but not in lung adenocarcinoma.
authors.affiliation: Medical School of Southeast University, 87 Dingjiaqiao Street, Nanjing, Jiangshu, 210009, PR China. tjl2004@sina.com
authors.forename: Jinlong
authors.initials: J
authors.lastname: Tong
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
authors.forename: Hongyan
authors.initials: H
authors.lastname: Cheng
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhen
authors.forename: Yuandong
authors.initials: Y
authors.lastname: Cao
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhu
authors.forename: Jianling
authors.initials: J
authors.lastname: Bai
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins