Sun Ding-Ping, Lin Ching-Yih, Tian Yu-Feng, Chen Li-Tzong, Lin Li-Ching, Lee Sung-Wei, Hsing Chung-Hsi, Lee Hao-Hsien, Shiue Yow-Ling, Huang Hsuan-Ying, Li Chien-Feng, Liang Peir-In
Division of General Surgery, Department of Surgery, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan.
Tumour Biol. 2013 Oct;34(5):3059-69. doi: 10.1007/s13277-013-0872-2. Epub 2013 May 31.
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.
胆囊癌（GBC）是一种相对罕见的疾病，其发病机制尚不清楚。人抗原R（HuR）是一种RNA结合蛋白，通过稳定或调节相应信使RNA的转录来调节各种癌症相关蛋白的表达。HuR在一大组胆囊癌中的表达意义尚待评估。总共选取了164例胆囊癌病例，并进行了HuR免疫染色。通过组织化学评分评估HuR核（HuR-N）表达和HuR胞质（HuR-C）表达。在161例有随访数据的患者中，将HuR表达结果与各种临床病理因素、疾病特异性生存（DSS）和无病生存（DFS）进行关联分析。HuR-N过表达与高组织学分级（p = 0.001）、血管侵犯（p < 0.001）和高Ki-67标记指数（p < 0.001）密切相关。HuR-C过表达与较高的原发肿瘤状态（p < 0.001）、晚期肿瘤分期（p < 0.001）、组织学类型（p = 0.006）、高组织学分级（p < 0.001）、血管和神经周围侵犯（分别为p < 0.001和p = 0.002）、肿瘤坏死（p = 0.042）以及高Ki-67标记指数（p = 0.002）显著相关。此外，HuR-C过表达还与HuR-N过表达（p < 0.001）和细胞周期蛋白A过表达（p = 0.026）相关。在单因素分析中，HuR-N过表达与较差的DFS相关（p = 0.0348），但在单因素（均p < 0.0001）和多因素（DSS，p = 0.006；DFS，p = 0.001）分析中，HuR-C过表达均与更差的DSS和DFS密切相关。HuR表达的亚细胞定位与胆囊癌的不同不良表型相关。此外，HuR-C过表达是DSS和DFS不佳的独立预后因素，提示其在肿瘤发生或致癌过程中的作用以及作为胆囊癌潜在预后标志物的意义。
