Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis.
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.
Chen
Yuan
Y
Institute of Pathology, University Hospital Charité, Humboldt-University, Schumannstrasse 20-21, D-10098 Berlin, Germany.
Knösel
Thomas
T
Kristiansen
Glen
G
Pietas
Agnieszka
A
Garber
Mitchell E
ME
Matsuhashi
Sachiko
S
Ozaki
Iwata
I
Petersen
Iver
I
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
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins