Article
Retinoid receptors in pancreatic cancer
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Authors
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Alexandr Bazhin
- Chirurgische Klinik, Allgemeine Chirurgie, Heidelberg
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Tim Bleul
- Chirurgische Klinik, Allgemeine Chirurgie, Heidelberg
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Markus W. Büchler
- Chirurgische Klinik, Allgemeine Chirurgie, Heidelberg
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Jens Werner
- Chirurgische Klinik, Allgemeine Chirurgie, Heidelberg
| Published: | April 26, 2013 |
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Outline
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Introduction: Pancreatic adenocarcinoma (PDAC) has a particularly poor prognosis with a median survival of 6 months. The standard treatment today is surgical resection and subsequent adjuvant chemotherapy. This is possible in about 20% of all patients, and results in a median survival of over 20 months. Retinoic acid is the major physiologically active form of vitamin A regulating the expression of different genes. To date two families of retinoid nuclear receptors are identified: retinoic acid receptors (RAR) and retinoid X receptors (RXR). At present little quantitative data is available concerning retinoid receptor expression in healthy pancreas compared to pancreatic carcinoma. The main aim of this work was to study comprehensively the retinoid receptor expression and evaluate its potential prognostic role in pancreatic cancer.
Material and methods: Expression of RAR and RXR subtypes (α and β) was quantified on RNA level in the human tumor tissues and in the murine PDAC samples using quantitative real-time PCR. Survival analysis was done using Kaplan-Meyer curves with subsequently Log rank test. For the predicative capacity estimation receiver operating characteristic (ROC) curve analysis was performed.
Results: RARα, RARβ, RXRα and RXRβ are significantly lower expressed in human and murine PDAC tissues when compared to healthy counterpart. PDAC patients with high RARα or RXRα show a significant longer survival as patients with low expression of the receptors. Decreased expression of RARα and RXRβ has been found in T3 and T4 patients compared to T1 and T2. Expression of the retinoid receptors is lower in N1 patients compared to N0. ROC curves demonstrate that the retinoid receptor expression is a good predictor for patient survival of more than 12 months after diagnosis and operation.
Conslusion: Our results show that PDAC cells express less retinoid receptors than their healthy counterparts. Decreased retinoid receptor expression is associated with poor survival and is a suitable prognostic marker for PDAC patients.
