Abstract | PURPOSE: EXPERIMENTAL DESIGN: Real-time quantitative reverse transcription-PCR was used to quantify tumor mRNA levels for Axl and Gas6 in a cohort (n = 221) of RCC patients. Serum levels of soluble sAxl and Gas6 proteins were measured using specific ELISA assays (n = 282). The presence of Axl protein in tumor tissue was evaluated by immunohistochemistry (n = 294). Results were correlated to tumor-associated variables, clinical biochemical tests, and patient survival. RESULTS:
Tumor Axl mRNA levels correlated independently to survival when assessed against tumor stage and grade. In the study group, the median cancer-specific survival of all RCC patients during 307 months of follow-up was 55 months (confidence interval, +/-40.4). The 25% of patients with lowest tumor Axl mRNA levels had significantly better survival than the rest (P = 0.0005), with 70% of the patients still alive at the end of follow-up. In contrast, in patients with medium-high Axl mRNA, only 25% were alive at the end of follow-up. Tumor Gas6 mRNA levels correlated to survival, tumor-associated variables, and disease severity as did serum levels of soluble sAxl and Gas6 protein. However, no correlation between Axl protein in tumor tissue and survival was found. CONCLUSIONS: Axl and Gas6 expression in RCC are associated with tumor advancement and patient survival. In particular, low tumor Axl mRNA levels independently correlated with improved survival.
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Authors | Anna Gustafsson, Danuta Martuszewska, Martin Johansson, Carl Ekman, Sassan Hafizi, Börje Ljungberg, Björn Dahlbäck |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 15
Issue 14
Pg. 4742-9
(Jul 15 2009)
ISSN: 1557-3265 [Electronic] United States |
PMID | 19567592
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intercellular Signaling Peptides and Proteins
- Oncogene Proteins
- Proto-Oncogene Proteins
- RNA, Messenger
- growth arrest-specific protein 6
- Receptor Protein-Tyrosine Kinases
- Axl Receptor Tyrosine Kinase
- AXL protein, human
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Carcinoma, Renal Cell
(genetics, metabolism, pathology)
- Disease Progression
- Enzyme-Linked Immunosorbent Assay
(statistics & numerical data)
- Female
- Follow-Up Studies
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Immunohistochemistry
(statistics & numerical data)
- Intercellular Signaling Peptides and Proteins
(blood, genetics, metabolism)
- Kaplan-Meier Estimate
- Kidney Neoplasms
(genetics, metabolism, pathology)
- Male
- Middle Aged
- Oncogene Proteins
(blood, genetics, metabolism)
- Prognosis
- Proportional Hazards Models
- Proto-Oncogene Proteins
- RNA, Messenger
(genetics, metabolism)
- Receptor Protein-Tyrosine Kinases
(blood, genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
(statistics & numerical data)
- Axl Receptor Tyrosine Kinase
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