Clusterin Expression Inversely Correlates with Chemosensitivity and Predicts Poor Survival in Patients with Locally Advanced Cervical Cancer Treated with Cisplatin-Based Neoadjuvant Chemotherapy and Radical Hysterectomy
Clusterin Expression Inversely Correlates with Chemosensitivity and Predicts Poor Survival in Patients with Locally Advanced Cervical Cancer Treated with Cisplatin-Based Neoadjuvant Chemotherapy and Radical Hysterectomy
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DOI：
10.1007/s12253-009-9235-0
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Sakuragi, Noriaki
中科院分区：
文献类型：
--
作者：
Watari, Hidemichi;Kanuma, Tatsuya;Sakuragi, Noriaki
clusterin是一种抗凋亡分子，其过表达可诱导多种癌细胞对化疗产生耐药性。本研究的目的是评估clusterin表达对预测以铂类为基础的新辅助化疗的反应和浸润性宫颈癌患者随后接受根治性子宫切除术的生存率的意义。新辅助化疗前的浸润性宫颈癌活检标本来自1994年至2007年在北海道大学医院和群马大学医院接受根治性子宫切除术的46例患者。采用免疫组化法检测clusterin蛋白的表达。结果进行了评价与几个临床病理因素。生存分析采用Kaplan-Meier曲线和对数秩检验。独立预后因素采用多因素考克斯回归分析。子宫颈癌细胞中的histerin蛋白主要表达于胞浆中。在分析的因素中，clusterin蛋白在新辅助化疗前宫颈癌组织中的表达与化疗疗效差显著相关。单因素分析显示化疗疗效（p=0.01）、淋巴结转移（p=0.02）和clusterin表达（p=0.02）与生存有关。多因素分析显示，淋巴结转移（p=0.03）和clusterin表达（p=0.03）是宫颈癌患者生存的独立预后因素。结论：clusterin表达可作为预测宫颈癌患者新辅助化疗和根治性子宫切除术后铂类化疗疗效和生存率的新分子标志物。
Overexpression of clusterin, an antiapoptotic molecule, has been reported to induce resistance to chemotherapy in a variety of cancer cell types. The aim of this study was to evaluate the significance of clusterin expression to predict response to platinum-based neoadjuvant chemotherapy and survival of patients with invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy specimens of invasive cervical cancer before neoadjuvant chemotherapy were obtained from 46 patients who subsequently underwent radical hysterectomy at Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007. The expression of clusterin protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed by 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 clusterin protein in cervical cancer tissues before neoadjuvant chemotherapy was significantly related to poor response to chemotherapy among factors analyzed. Univariate analysis on prognostic factors showed that response to chemotherapy (p=0.01), lymph node metastasis (p=0.02), and clusterin expression (p=0.02) were related to survival. Multivariate analysis revealed that lymph node metastasis (p=0.03), and clusterin expression (p=0.03) were independent prognostic factors for survival of cervical cancer patients. We conclude that clusterin expression could be a new molecular marker to predict response to platinum-based chemotherapy and survival of patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy.