Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy
Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy
复制标题
DOI：
10.1007/s40291-017-0255-2
复制
发表时间：
2017-04-01
影响因子：
4
通讯作者：
Fujiwara, Keiichi
中科院分区：
文献类型：
--
作者：
Hanaoka, Tatsuya;Hasegawa, Kosei;Fujiwara, Keiichi
背景细胞表面糖蛋白间皮素（mesothelin）在多种恶性疾病中高度表达。正常间皮素的表达仅限于间皮细胞内衬胸膜，腹膜和心包，使其成为一个生物标志物和一个有吸引力的目标为cancer therapeutic.Methods我们研究了肿瘤间皮素的表达和血清间皮素水平与上皮性卵巢癌或交界性肿瘤患者。在过去的前瞻性研究中，共161例患者进行了分析，肿瘤间皮素的表达使用免疫组化和血清间皮素的表达使用酶联免疫吸附试验。结果88（68.8%）上皮性卵巢癌和8（24.2%）交界性肿瘤表现出高间皮素表达，这是与较短的无进展生存期和总生存期。上皮性卵巢癌患者肿瘤间皮素表达状态与血清间皮素水平中度相关。基于受试者操作特征分析，血清间皮素水平高于2.20 nM预测上皮性卵巢癌患者的肿瘤间皮素表达较高（曲线下面积= 0.81）。在45例复发性上皮性卵巢癌患者中，我们观察到与初步诊断时的水平相比，血清间皮素水平相对较低。我们还跟踪了二线化疗过程中血清间皮素水平的变化，发现在一些患者的临床反应和血清间皮素的变化之间的差异，这表明肿瘤细胞之间的异质性与或不与间皮素expression.Conclusion血清间皮素可能是一个有用的非侵入性生物标志物替代肿瘤间皮素表达在未来的临床试验间皮素靶向治疗。
Background The cell surface glycoprotein mesothelin is highly expressed in several malignant diseases. Normal mesothelin expression is limited to mesothelial cells lining the pleura, peritoneum, and pericardium, making it a biomarker and an attractive target for cancer therapy.Methods We investigated tumor mesothelin expression and serum mesothelin levels in patients with epithelial ovarian cancer or borderline tumors. In total, 161 patients selected from a previous prospective study were analyzed for tumor mesothelin expression using immunohistochemistry and serum mesothelin expression using enzyme-linked immunosorbent assay.Results Eighty-eight (68.8%) epithelial ovarian cancers and eight (24.2%) borderline tumors showed high mesothelin expression, which was associated with shorter progression-free and overall survival. The tumor mesothelin expression status was moderately correlated with serum mesothelin levels in epithelial ovarian cancer patients. Based on receiver operating characteristic analysis, a serum mesothelin level above 2.20 nM predicted high tumor mesothelin expression in epithelial ovarian cancer patients (area under the curve = 0.81). In 45 patients with recurrent epithelial ovarian cancer, we observed relatively lower levels of serum mesothelin, compared to the level at the primary diagnosis. We also tracked the change in the serum mesothelin level during the course of second-line chemotherapy and found a discrepancy between the clinical response and the serum mesothelin change in some patients, which suggested tumor heterogeneity among the tumor cells with or without mesothelin expression.Conclusion Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.