Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer
Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer
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DOI：
10.1007/s00262-011-1010-x
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
Vlad, Anda M.
中科院分区：
文献类型：
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作者：
Budiu, Raluca A.;Mantia-Smaldone, Gina;Vlad, Anda M.
MUC1 (CA15-3) 和 MUC16 (CA125) 肿瘤相关抗原在卵巢癌中表达上调，并且可以通过标准化测试在患者血清中检测到。我们假设增加的 MUC1 和 MUC16 抗原会增强铂耐药卵巢癌患者的抗体反应，并且这些反应的频率和强度可以用作治疗反应和疾病结果的免疫生物标志物。我们通过免疫组织化学 (IHC) 测量了 MUC1 和 MUC16 肿瘤表达，通过 ELISA 评估了 28 名患有铂耐药或铂难治性卵巢癌的卵巢癌患者的血清抗原水平并定量了循环抗体，并接受腹膜内 (IP) 白细胞介素 2 (IL-2) 治疗。 MUC1 和 MUC16 在肿瘤样本中过度表达，并表现出差异分布特征。所有患者的血清 MUC1 (CA15-3) 测量值均升高，并且与死亡风险增加显着相关 (P = 0.003)。分别在 92% 和 50% 的病例中发现了 MUC1 特异性 IgM 和 IgG 抗体。在 IP IL-2 治疗期间的早期 (P = 0.025) 和晚期 (P = 0.022) 时间点，进展性疾病患者的平均抗 MUC1 IgG 均值高于应答者。抗 MUC1 IgM 抗体与早期 (P = 0.052) 和晚期 (P = 0.009) 时间点的总生存率呈负相关。与 MUC1 相比，在本研究中，可溶性 MUC16 和 MUC16 特异性抗体均与临床反应或总生存期没有显着相关。血清 MUC1 升高和抗 MUC1 抗体水平升高预示着铂类耐药或铂类难治性卵巢癌临床反应不佳和总生存期降低。
MUC1 (CA15-3) and MUC16 (CA125) tumor-associated antigens are upregulated in ovarian cancer and can be detected in patients' sera by standardized tests. We postulated that increased MUC1 and MUC16 antigens augment antibody responses in platinum-resistant ovarian cancer patients and that the frequency and intensity of these responses can be used as immune biomarkers of treatment response and disease outcome. We measured MUC1 and MUC16 tumor expression by immunohistochemistry (IHC), assessed serum antigenic levels and quantitated circulating antibodies by ELISA in a cohort of 28 ovarian cancer patients with platinum-resistant or platinum-refractory ovarian cancer, and treated with intraperitoneal (IP) interleukin-2 (IL-2). MUC1 and MUC16 were overexpressed in tumor samples and showed differential distribution profiles. Serum MUC1 (CA15-3) measurements were elevated in all patients and significantly correlated with increased risk of death (P = 0.003). MUC1-specific IgM and IgG anitbodies were found in 92 and 50% of cases, respectively. Patients with progressive disease had higher mean anti-MUC1 IgG than responders at both early (P = 0.025) and late (P = 0.022) time points during IP IL-2 treatment. Anti-MUC1 IgM antibodies inversely correlated with overall survival at both early (P = 0.052) and late (P = 0.009) time points. In contrast to MUC1, neither soluble MUC16 nor MUC16-specific antibodies were significantly associated with clinical response or overall survival in this study. Increased serum MUC1 and high anti-MUC1 antibody levels are prognostic for poor clinical response and reduced overall survival in platinum-resistant or platinum-refractory ovarian cancer.