Osteopontin as a potential diagnostic biomarker for ovarian cancer
Osteopontin as a potential diagnostic biomarker for ovarian cancer
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DOI：
10.1001/jama.287.13.1671
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发表时间：
2002-04-03
影响因子：
120.7
通讯作者：
Mok, SC
中科院分区：
文献类型：
--
作者：
Kim, JH;Skates, SJ;Mok, SC
背景：需要开发新的卵巢癌生物标志物用于早期检测和疾病监测。利用互补DNA（cDNA）微阵列数据进行分析，可用于鉴定癌细胞中上调表达的基因，其产物可作为潜在的生物标志物进一步验证。目的描述骨桥蛋白（osteopontin）上调表达基因的验证研究，该基因以前是用cDNA微阵列系统鉴定的。实验和横断面研究涉及卵巢癌和健康人卵巢表面上皮细胞系和培养物，1992年6月至2001年6月收集的存档石蜡包埋卵巢组织，以及1992年6月至2001年6月在美国2个学术机构的妇科肿瘤服务中评估盆腔肿块的144名患者的新鲜组织和术前血浆。从1992年5月至1997年3月开始的卵巢癌流行病学研究中选择107名妇女的血浆样本作为健康对照，主要结果测量癌细胞和新鲜卵巢组织中信使RNA的相对表达，通过实时聚合酶链反应测量，（-DeltaDeltaCT）（代表骨桥蛋白表达量的定量值）;骨桥蛋白产生，用免疫组织化学研究在卵巢健康和肿瘤组织中定位和评分;结果骨桥蛋白在5个健康卵巢上皮细胞培养物中表达的2（-DeltaDeltaCT）的几何平均值为4.1，而在14个卵巢癌细胞系中为270.4（P= 0.03）。骨桥蛋白表达的几何平均值2（-DeltaDeltaCT）在2例健康卵巢上皮组织样本中为9.0，而在27例显微切割卵巢肿瘤组织样本中为164.0（P= 0.06）。骨桥蛋白的免疫定位显示，61例浸润性卵巢癌患者和29例交界性卵巢肿瘤患者的组织样本表达的骨桥蛋白水平高于6例良性肿瘤患者的组织样本和3例健康卵巢上皮样本（P= 0.03）。血浆骨桥蛋白水平明显升高（P
Context Development of new biomarkers for ovarian cancer is needed for early detection and disease monitoring. Analyses involving complementary DNA (cDNA) microarray data can be used to identify up-regulated genes in cancer cells, whose products may then be further validated as potential biomarkers.Objective To describe validation studies of an up-regulated gene known as osteopontin, previously identified using a cDNA microarray system.Design, Setting, and Participants Experimental and cross-sectional studies were conducted involving ovarian cancer and healthy human ovarian surface epithelial cell lines and cultures, archival paraffin-embedded ovarian tissue collected between June 1992 and June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated for a pelvic mass between June 1992 and June 2001 in gynecologic oncology services at 2 US academic institutions. Plasma samples from 107 women selected from an epidemiologic study of ovarian cancer initiated between May 1992 and March 1997 were used as healthy controls.Main Outcome Measures Relative messenger RNA expression in cancer cells and fresh ovarian tissue, measured by real-time polymerase chain reaction as 2(-DeltaDeltaCT) (a quantitative value representing the amount of osteopontin expression); osteopontin production, localized and scored in ovarian healthy and tumor tissue with immunohistochemical studies; and amount of osteopontin in patient vs control plasma, measured using an enzyme-linked immunoassay.Results The geometric mean for 2(-DeltaDeltaCT) for osteopontin expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared with 270.4 in 14 ovarian cancer cell lines (P=.03). The geometric mean 2(-DeltaDeltaCT) for osteopontin expression in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with 164.0 in 27 microdissected ovarian tumor tissue samples (P=.06). Immunolocalization of osteopontin showed that tissue samples from 61 patients with invasive ovarian cancer and 29 patients with borderline ovarian tumors expressed higher levels of osteopontin than tissue samples from 6 patients with benign tumors and samples of healthy ovarian epithelium from 3 patients (P=.03). Osteopontin levels in plasma were significantly higher (P