Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Int J Gynecol Cancer. 2012 Mar;22(3):465-70. doi: 10.1097/IGC.0b013e31821a03d9.
Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT.
Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis.
Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival.
We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.
已有研究报道，聚集蛋白（CLU）作为一种抗凋亡分子，其过表达可诱导多种癌细胞类型对放射治疗（RT）产生耐药性。本研究旨在评估CLU 表达对接受根治性 RT 的晚期宫颈癌患者生存的预测意义。
本研究纳入了 1998 年至 2008 年在北海道大学医院接受治疗且病历资料完整的 34 例接受根治性 RT 的晚期宫颈癌患者的活检组织标本。采用免疫组织化学法分析 CLU 蛋白的表达情况。评估结果与多种临床病理因素相关。采用 Kaplan-Meier 曲线和对数秩检验进行生存分析。采用多因素 Cox 回归分析确定独立预后因素。
CLU 蛋白主要存在于宫颈癌细胞的细胞质中。在接受根治性 RT 之前的宫颈癌组织中，CLU 蛋白的表达与分析的任何临床病理因素均无显著相关性，包括年龄、临床分期、组织学类型和对 RT 的反应。对预后因素的单因素分析显示，组织学类型（P=0.001）和 CLU 表达（P=0.02）与生存有关。多因素分析显示，组织学类型（P=0.002）和 CLU 表达（P=0.02）均是总生存的独立预后因素。
我们的结论是，CLU 可能成为预测接受根治性 RT 的晚期宫颈癌患者总生存的新的分子标志物。
