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

Ding Ping Sun, Ching Yih Lin, Yu Feng Tian, Li Tzong Chen, Li Ching Lin, Sung Wei Lee, Chung Hsi Hsing, Hao Hsien Lee, Yow Ling Shiue, Hsuan Ying Huang, Chien Feng Li, Peir In Liang

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18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3059-3069
Number of pages11
JournalTumor Biology
Issue number5
Publication statusPublished - 2013


  • Gallbladder cancer
  • HuR protein
  • Immunohistochemistry
  • Protein localization

ASJC Scopus subject areas

  • Cancer Research


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