title: Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis.
abstract: The programmed cell death 4 gene (PDCD4), a newly identified transformation suppressor, was analysed in lung tumour cell lines and primary lung carcinomas. Reduced PDCD4 mRNA expression was observed in two immortalized lung cell lines and 18 cancer cell lines by northern blot analysis. In the survey of primary lung tumours, PDCD4 cDNA was poorly represented in 47 lung tumours compared with normal lung tissue by cDNA microarray analysis and this poor representation was significantly associated with high-grade (G3) adenocarcinomas (p = 0.012). Immunohistochemical analysis of 124 primary carcinomas comprising all subtypes demonstrated that PDCD4 protein expression was widely lost in tumour samples (83%) and was negatively related to poor prognosis (p = 0.013). The loss of PDCD4 expression correlated with higher grade and disease stage (p = 0.045 and 0.034, respectively), but not tumour size and nodal status. Similarly to the cDNA data, lack of PDCD4 expression was significantly linked to tumour grade in adenocarcinoma (n = 59, p = 0.048), while in squamous cell carcinoma (n = 58), no relationship between PDCD4 expression and clinicopathological parameters was established. These data suggest that the loss of PDCD4 expression is a prognostic factor in lung cancer and may correlate with tumour progression.
authors.affiliation: Institute of Pathology, University Hospital Charité, Humboldt-University, Schumannstrasse 20-21, D-10098 Berlin, Germany.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pietas
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Garber
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuhashi
authors.forename: Iwata
authors.initials: I
authors.lastname: Ozaki
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins