State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Cancer Sci. 2009 Dec;100(12):2354-60. doi: 10.1111/j.1349-7006.2009.01349.x. Epub 2009 Sep 4.
Clusterin (CLU) is frequently overexpressed and correlates closely with chemotherapy and radiotherapy resistance and poor prognosis in many human cancers. However, the significance of CLU expression in chemoradiotherapy (CRT) sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma (ESCC) are still unknown. In the present study, we used the methods of immunohistochemistry and terminal deoxyuridine triphosphate nick-end labeling assay to examine the expression status of CLU and apoptotic index in 110 pretreated biopsy specimens of ESCC patients treated with definitive CRT. High expression of CLU was observed in 42.7% of epithelium and 50.0% of stroma in ESCC. A significant association of high CLU stromal expression with large tumor size (P = 0.012) and locoregional progression (P = 0.001) was observed, and high epithelial expression of CLU showed a significant correlation with the lack of complete response (P = 0.028) and low apoptotic index (P = 0.001). Univariate analysis revealed that high CLU stromal expression was associated with poor locoregional progression-free survival, distant progression-free survival, and overall survival. Furthermore, ESCC patients with high CLU expression in both epithelium and stroma have the shortest survival time among the subgroups of different CLU expression status. In multivariate analysis, CLU stromal expression was evaluated as an independent prognostic factor for locoregional progression-free survival, distant progression-free survival, and overall survival. These findings suggest an important role for CLU, especially in stroma, in ESCC progression, and that high CLU epithelial expression might be a promising predictor of ESCC resistance to CRT.
簇集蛋白（CLU）在许多人类癌症中经常过表达，与化疗和放疗抵抗及预后不良密切相关。然而，CLU 在放化疗（CRT）敏感性中的表达意义及其对食管鳞状细胞癌（ESCC）预后的影响尚不清楚。在本研究中，我们使用免疫组织化学和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法检测了 110 例接受根治性 CRT 的 ESCC 患者预处理活检标本中 CLU 的表达状态和凋亡指数。在 ESCC 中，CLU 在 42.7%的上皮和 50.0%的基质中高表达。CLU 高表达与肿瘤较大（P = 0.012）和局部区域进展（P = 0.001）显著相关，而 CLU 上皮高表达与完全缓解缺乏（P = 0.028）和低凋亡指数（P = 0.001）显著相关。单因素分析显示，CLU 基质高表达与局部区域无进展生存率、远处无进展生存率和总生存率降低相关。此外，在不同 CLU 表达状态的亚组中，CLU 在上皮和基质中均高表达的 ESCC 患者的生存时间最短。多因素分析显示，CLU 基质表达被评估为局部区域无进展生存率、远处无进展生存率和总生存率的独立预后因素。这些发现表明 CLU 特别是在基质中在 ESCC 进展中起重要作用，并且 CLU 上皮高表达可能是 ESCC 对 CRT 抵抗的有前途的预测因子。
