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检测恶性腹水中的可溶性上皮细胞黏附分子(sEpCAM)可预测接受卡妥索单抗治疗患者的总生存期较差。

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab.

作者信息

Seeber Andreas, Braicu Ioana, Untergasser Gerold, Nassir Mani, Fong Dominic, Botta Laura, Gastl Guenther, Fiegl Heidi, Zeimet Alain, Sehouli Jalid, Spizzo Gilbert

机构信息

Department of Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria.

Tyrolean Cancer Research Institute, Innsbruck, Austria.

出版信息

Oncotarget. 2015 Sep 22;6(28):25017-23. doi: 10.18632/oncotarget.4496.

Abstract

EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer patients with malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from catumaxomab. Recent data showed that soluble EpCAM (sEpCAM) is capable to block the effect of catumaxomab in vitro. This exploratory retrospective analysis was performed on archived ascites samples to evaluate the predictive role of sEpCAM in catumaxomab-treated patients. Sixty-six catumaxomab-treated patients with an available archived ascites sample were included in this study and tested for sEpCAM by sandwich ELISA. All probes were sampled before treatment start and all patients received at least one catumaxomab infusion. Overall survival, puncture-free survival and time to next puncture were compared between sEpCAM-positive and -negative patients. We detected sEpCAM in ascites samples of 9 patients (13.6%). These patients showed a significantly shorter overall survival. The prognostic significance of sEpCAM in ascites was particularly strong in patients with ovarian cancer. Puncture-free survival and time to next puncture were not significantly different between sEpCAM-positive and -negative patients. We propose sEpCAM in malignant ascites as a potential predictive marker in cancer patients treated with catumaxomab. Prospective studies with larger patients samples are urgently needed to confirm these findings and studies testing dose-intensified catumaxomab in patients with sEpCAM-positive ascites should be envisaged.

摘要

上皮细胞黏附分子(EpCAM)是癌症治疗的一个有吸引力的靶点,EpCAM特异性抗体卡妥索单抗已被用于腹腔内治疗伴有恶性腹水的EpCAM阳性癌症患者。需要新的预后标志物来选择最能从卡妥索单抗治疗中获益的患者。最近的数据表明,可溶性EpCAM(sEpCAM)在体外能够阻断卡妥索单抗的作用。本探索性回顾性分析对存档的腹水样本进行,以评估sEpCAM在接受卡妥索单抗治疗患者中的预测作用。本研究纳入了66例接受卡妥索单抗治疗且有可用存档腹水样本的患者,并通过夹心酶联免疫吸附测定法检测sEpCAM。所有样本均在治疗开始前采集,所有患者均接受了至少一次卡妥索单抗输注。比较了sEpCAM阳性和阴性患者的总生存期、无穿刺生存期和下次穿刺时间。我们在9例患者(13.6%)的腹水样本中检测到了sEpCAM。这些患者的总生存期明显较短。sEpCAM在腹水中的预后意义在卵巢癌患者中尤为显著。sEpCAM阳性和阴性患者的无穿刺生存期和下次穿刺时间无显著差异。我们提出,恶性腹水中的sEpCAM可作为接受卡妥索单抗治疗的癌症患者的潜在预测标志物。迫切需要开展更大样本量患者的前瞻性研究来证实这些发现,并且应设想针对sEpCAM阳性腹水患者进行卡妥索单抗剂量强化试验的研究。

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