Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Clin Biochem. 2013 Oct;46(15):1462-8. doi: 10.1016/j.clinbiochem.2013.03.010. Epub 2013 Mar 23.
Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women.
FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate.
FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125.
FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.
卵巢癌是北美最致命的妇科恶性肿瘤。尽管在疾病早期诊断时存活率较高，但在晚期诊断时则呈指数下降。因此，需要新型的早期检测生物标志物。通过结合蛋白质组学、转录组学和生物信息学的卵巢癌生物标志物发现的综合方法，我们的实验室已经确定了叶酸受体 1（FOLR1）和 Dickkopf 相关蛋白 3（Dkk-3）作为潜在的生物标志物。本研究的目的是测量卵巢癌、良性妇科疾病和健康女性患者血清中的 FOLR1 和 Dkk-3 水平。
使用酶联免疫吸附测定（ELISA）分析了 100 例卵巢癌患者、100 例良性妇科疾病患者和 100 例健康女性的血清中的 FOLR1 和 Dkk-3。所有标本均进行了三次重复分析。
与健康对照组（P<0.0001）和良性妇科疾病患者（P<0.0001）相比，卵巢癌患者血清中的 FOLR1 明显升高。此外，FOLR1 与 CA125 呈强相关性，因为两者在浆液性组织类型和晚期疾病中均升高。在接受者操作特征曲线分析中，FOLR1 并不优于 CA125，并且两种标志物之间没有明显的互补性。Dkk-3 在三组血清中没有显著差异，与 CA125 也没有相关性。
FOLR1 是一种新的卵巢癌生物标志物，与 CA125 密切相关。FOLR1 在卵巢癌发病机制中的作用值得进一步研究。
