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Published on: September 25, 2018
Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis
Yuan Chen1, Thomas Knösel, Glen Kristiansen
1Institute of Pathology, University Hospital Charité, Humboldt-University, Schumannstrasse 20-21, D-10098 Berlin, Germany.
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.
Insights
Loss of programmed cell death 4 gene (PDCD4) expression is common in lung cancer. Reduced PDCD4 indicates a poorer prognosis and correlates with higher tumor grade and stage, suggesting its role in lung cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Programmed cell death 4 (PDCD4) is a known tumor suppressor gene.
- Its role in lung cancer progression and prognosis requires further elucidation.
Purpose of the Study:
- To investigate the expression levels of PDCD4 in lung tumor cell lines and primary lung carcinomas.
- To determine the correlation between PDCD4 expression and clinicopathological features, including tumor grade, stage, and patient prognosis.
Main Methods:
- Northern blot analysis was used to assess PDCD4 mRNA expression in lung cell lines.
- cDNA microarray analysis compared PDCD4 representation in primary lung tumors versus normal lung tissue.
- Immunohistochemical analysis evaluated PDCD4 protein expression in 124 primary lung carcinomas.
Main Results:
- Reduced PDCD4 mRNA expression was detected in lung cancer cell lines.
- PDCD4 cDNA was significantly underrepresented in primary lung tumors, particularly in high-grade adenocarcinomas.
- PDCD4 protein expression was lost in 83% of primary lung carcinomas and negatively correlated with poor prognosis.
- Loss of PDCD4 expression was associated with higher tumor grade and disease stage, but not tumor size or nodal status.
Conclusions:
- Loss of PDCD4 expression is a frequent event in lung cancer.
- Reduced PDCD4 expression serves as a significant prognostic factor in lung cancer.
- PDCD4 may play a role in the progression of lung tumors, especially adenocarcinomas.
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