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. Copyright © 2003 John Wiley & Sons, Ltd.
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PDCD4 protein expression is often down-regulated in tumors but is maintained at high levels in a large number of tumors.
“The expression of PDCD4-protein is often down-regulated in the tumors [17,18,19,20] but is maintained in high levels in a large number of tumors.”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [17]
PDCD4 mRNA levels are decreased in many cancer tissues and cell lines as compared with corresponding normal tissues.
“PDCD4 mRNA levels are decreased in many cancer tissues and cell lines as compared with the corresponding normal tissues [17,19,20].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [17]
Loss of PDCD4 expression is correlated with poor prognosis and survival in breast cancer, colorectal cancer, lung cancer, ovarian cancer, and renal cell carcinoma.
“the loss of PDCD4 expression is correlated with poor prognosis and survival in breast cancer [89], colorectal cancer [90], lung cancer [17], ovarian cancer [91] and renal cell carcinoma [92] (Table 2).”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [17]
PDCD4 loss is diagnostic for human cancer staging and prognostic for survival in colon, lung, liver, breast, glioma and esophageal cancers.
“its loss is diagnostic for human cancer staging and prognostic for survival in colon, lung, liver, breast, glioma and esophageal cancers (6–11).”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [7]
Loss of PDCD4 expression in human lung cancer correlates with higher grade and disease stage.
“Loss of PDCD4 expression in human lung cancer correlates with higher grade and disease stage (Chen et al., 2003).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Chen et al., 2003
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References 24 · Cited by 265
- Authors
- Chen, Y., Knösel, T., Kristiansen, G., Pietas, A., Garber, M. E., Matsuhashi, S., Ozaki, I., & Petersen, I.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Stanford Medicine (US)
- Saga University (JP)
- Corresponding author
- Petersen, Iver
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2003-03-31
- Volume
- 200
- Issue
- 5
- Pages
- 640-646
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2042812307
- Cited by
- 265
- References
- 24
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 9 · 2021: 15 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 12 · 2016: 20 · 2015: 12 · 2014: 17 · 2013: 13 · 2012: 18
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- German Cancer Society (Deutsche Krebshilfe)
- German Research Foundation (DFG)
- Topics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- PDCD4, lung cancer, tumor suppressor, gene expression loss, tumor progression, prognosis, tumor grade, adenocarcinoma, squamous cell carcinoma, disease stage, prognostic factors
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lung Neoplasms, Middle Aged, Neoplasm Proteins, Prognosis, RNA, Messenger, RNA, Neoplasm, Tumor Cells, Cultured, Biomarkers, Tumor, Blotting, Northern, Gene Expression, Survival Analysis, RNA-Binding Proteins, Disease Progression, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Apoptosis Regulatory Proteins
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