Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.
Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.
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DOI：
10.1371/journal.pone.0165609
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Miyagi E
中科院分区：
文献类型：
--
作者：
Arakawa N;Kobayashi H;Yonemoto N;Masuishi Y;Ino Y;Shigetomi H;Furukawa N;Ohtake N;Miyagi Y;Hirahara F;Hirano H;Miyagi E
卵巢透明细胞癌（CCC）是上皮性卵巢癌（EOC）的一种高致死性组织学亚型，目前尚无可靠的血清生物标志物。以前，使用基于蛋白质组的方法，我们确定了组织因子途径抑制物2（TFPI 2）作为CCC的候选血清生物标志物。在这项研究中，我们试图评估TFPI 2在CCC术前预测中的临床诊断性能。血清TFPI 2水平测定来自回顾性训练集的血清样品，所述训练集由患有良性和交界性卵巢肿瘤、EOC亚型和子宫疾病的患者组成。通过受试者工作特征（ROC）分析，我们比较了TFPI 2和CA 125在区分卵巢CCC患者与其他患者组方面的诊断性能。在前瞻性验证集中检查观察到的诊断性能。268名患者的训练集包括29名卵巢CCC患者。与子宫内膜异位症和几种EOC亚型患者中也升高的CA 125不同，血清TFPI 2水平仅在卵巢CCC患者中特异性升高，与肿瘤组织中的mRNA表达模式一致。TFPI 2的ROC曲线下面积（AUC）明显高于CA 125（AUC = 0.891 vs.0.595）。应用280 pg/mL的临界值，TFPI 2可以区分早期（FIGO I和II）CCC与子宫内膜异位症，敏感性为72.2%，特异性为93.3%，准确性为88.8%。在一个独立的156例患者前瞻性验证集中证实了类似的结果。TFPI 2是CCC术前诊断的一个有用的血清标志物。
There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.