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The Expression of Both Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 in Tissues Is Associated with Poor Prognosis in Colorectal Cancer Patients

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Abstract

Background

The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial.

Aims

We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC.

Methods

We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied.

Results

The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (−)/COX-2 (+), PPAR δ (+)/COX-2 (−), and PPAR δ (−)/COX-2 (−) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p < 0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR = 7.108, 95% CI 1.231–41.029, p = 0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p < 0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (−), CXCR4 (−)/VEGF-A (+), and CXCR4 (−)/VEGF-A (−) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p < 0.01).

Conclusions

The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.

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Acknowledgments

The authors thank Dr. Koji Yoshikawa (Department of pathology, National Hospital Organization Beppu Medical Center, Oita, Japan), Mr. Hitoshi Watanabe (Bioscience Education and Research Center, Akita University, Akita, Japan), and the pathological staff of both of the Beppu Medical Center (Oita, Japan) and Kyodo Byori, Inc. (Hyogo, Japan) for their useful suggestions and technical support about immunohistochemistry. There are no financial disclosures and potential conflicts of interest from any authors.

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Authors and Affiliations

  1. Department of Gastroenterology, Hepatology, and Nutrition, National Hospital Organization Beppu Medical Center, 1473 Uchikamado, Beppu, Oita, 874-0011, Japan

    Masahiro Yoshinaga, Kentaro Taki, Shinichi Somada, Yumiko Sakiyama, Norihiko Kubo, Toyoma Kaku, Satoru Tsuruta & Hironori Sakai

  2. Department of Clinical Research, National Hospital Organization Beppu Medical Center, Oita, Japan

    Masahiro Yoshinaga & Tetsuya Kusumoto

  3. Department of Surgery, National Hospital Organization Beppu Medical Center, Oita, Japan

    Tetsuya Kusumoto & Yoichi Muto

  4. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Kazuhiko Nakamura & Ryoichi Takayanagi

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  1. Masahiro Yoshinaga
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  2. Kentaro Taki
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Correspondence to Masahiro Yoshinaga.

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Yoshinaga, M., Taki, K., Somada, S. et al. The Expression of Both Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 in Tissues Is Associated with Poor Prognosis in Colorectal Cancer Patients. Dig Dis Sci 56, 1194–1200 (2011). https://doi.org/10.1007/s10620-010-1389-9

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  • DOI: https://doi.org/10.1007/s10620-010-1389-9

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