Hanaoka Tatsuya, Hasegawa Kosei, Kato Tomomi, Sato Sho, Kurosaki Akira, Miyara Akiko, Nagao Shoji, Seki Hiroyuki, Yasuda Masanori, Fujiwara Keiichi
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Mol Diagn Ther. 2017 Apr;21(2):187-198. doi: 10.1007/s40291-017-0255-2.
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.
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.
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.
Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.
细胞表面糖蛋白间皮素在多种恶性疾病中高表达。正常间皮素表达仅限于胸膜、腹膜和心包膜的间皮细胞，这使其成为一种生物标志物以及癌症治疗的一个有吸引力的靶点。
我们调查了上皮性卵巢癌或交界性肿瘤患者的肿瘤间皮素表达及血清间皮素水平。总共对先前一项前瞻性研究中选取的161例患者进行了分析，采用免疫组织化学检测肿瘤间皮素表达，采用酶联免疫吸附测定法检测血清间皮素表达。
88例（68.8%）上皮性卵巢癌和8例（24.2%）交界性肿瘤显示间皮素高表达，这与无进展生存期和总生存期缩短相关。上皮性卵巢癌患者的肿瘤间皮素表达状态与血清间皮素水平呈中度相关。基于受试者工作特征分析，血清间皮素水平高于2.20 nM可预测上皮性卵巢癌患者肿瘤间皮素高表达（曲线下面积 = 0.81）。在45例复发性上皮性卵巢癌患者中，我们观察到血清间皮素水平相较于初次诊断时相对较低。我们还追踪了二线化疗过程中血清间皮素水平的变化，发现部分患者的临床反应与血清间皮素变化之间存在差异，这提示了间皮素表达或未表达的肿瘤细胞之间存在肿瘤异质性。
在未来针对间皮素靶向治疗的临床试验中，血清间皮素可能是一种有用的非侵入性生物标志物替代物，用于评估肿瘤间皮素表达。
