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Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression

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Tumor Biology

Abstract

Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.

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Acknowledgments

This work was supported by grants from the National Science Council, Taiwan (NSC101-2320-B-384-001-MY3), the Department of Health, Taiwan (100-TMP-009-3 and DOH101-TD-C-111-004), and the Chi-Mei Medical Center, Tainan, Taiwan (100CM-TMU-01).

Conflicts of interest

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Author information

Authors and Affiliations

  1. Division of General Surgery, Department of Surgery, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan

    Ding-Ping Sun & Yu-Feng Tian

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan

    Ching-Yih Lin

  3. Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, 1, University Road, Tainan City, 701, Taiwan

    Li-Tzong Chen

  4. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100, Tzyou 1st Rd., Kaohsiung, 807, Taiwan

    Li-Tzong Chen & Li-Ching Lin

  5. Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, 201, Taikang, Taikang Vil., Liuying Dist., Tainan City, 736, Taiwan

    Sung-Wei Lee

  6. Department of Anesthesiology, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan

    Chung-Hsi Hsing

  7. Department of Surgery, Chi-Mei Medical Center, Liouying, 201, Taikang, Taikang Vil., Liuying Dist., Tainan City, 736, Taiwan

    Hao-Hsien Lee

  8. Institute of Biomedical Science, National Sun Yat-Sen University, 70, Lienhai Rd., Kaohsiung, 804, Taiwan

    Yow-Ling Shiue

  9. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123, Ta-pei Rd., Niao-Sung Dist., Kaohsiung, 833, Taiwan

    Hsuan-Ying Huang

  10. Department of Pathology, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan

    Chien-Feng Li & Peir-In Liang

  11. Department of Pharmacy, Chia Nan University of Pharmacy & Science, 60, Sec 1 Erren Roadm Rende Disctrict, Tainan City, 717, Taiwan

    Ding-Ping Sun

  12. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, 1, Nan-Tai Street, Yongkang Dist., Tainan City, 710, Taiwan

    Ching-Yih Lin

  13. Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, 60, Sec 1 Erren Roadm Rende Disctrict, Tainan City, 717, Taiwan

    Yu-Feng Tian

  14. National Institute of Cancer Research, National Health Research Institutes, 367 Shengli Rd., Tainan City, 704, Taiwan

    Li-Tzong Chen & Chien-Feng Li

  15. Department of Internal Medicine, National Cheng Kung University Hospital, 138, Shengli Rd., Tainan City, 704, Taiwan

    Li-Tzong Chen

  16. College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei City, 110, Taiwan

    Chung-Hsi Hsing

  17. Department of Biotechnology, Southern Taiwan University of Science and Technology, 1, Nan-Tai Street, Yongkang Dist., Tainan City, 710, Taiwan

    Chien-Feng Li

  18. Department of Medical Technology, Chung Hwa University of Medical Technology, 89, Wenhwa 1st St., Rende Dist., Tainan City, 717, Taiwan

    Chien-Feng Li

  19. Department of Pathology, Chi-Mei Medical Center, Liouying, 201, Taikang, Taikang Vil., Liuying Dist., Tainan City, 736, Taiwan

    Chien-Feng Li & Peir-In Liang

  20. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100, Tzyou 1st Rd., Kaohsiung, 807, Taiwan

    Peir-In Liang

Authors
  1. Ding-Ping Sun
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  2. Ching-Yih Lin
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  3. Yu-Feng Tian
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  5. Li-Ching Lin
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  6. Sung-Wei Lee
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  7. Chung-Hsi Hsing
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  8. Hao-Hsien Lee
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  9. Yow-Ling Shiue
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  10. Hsuan-Ying Huang
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  11. Chien-Feng Li
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  12. Peir-In Liang
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Correspondence to Peir-In Liang.

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Sun, DP., Lin, CY., Tian, YF. et al. Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression. Tumor Biol. 34, 3059–3069 (2013). https://doi.org/10.1007/s13277-013-0872-2

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  • DOI: https://doi.org/10.1007/s13277-013-0872-2

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