Simon Iris, Katsaros Dionyssios, Rigault de la Longrais Irene, Massobrio Marco, Scorilas Andreas, Kim Nam W, Sarno Mark J, Wolfert Robert L, Diamandis Eleftherios P
diaDexus, Inc., 343 Oyster Point Blvd., South San Francisco, CA, USA.
Gynecol Oncol. 2007 Aug;106(2):334-41. doi: 10.1016/j.ygyno.2007.03.035. Epub 2007 May 11.
This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125.
Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested. The marker concentrations were correlated with CA125 expression, clinicopathological variables, and patient outcome.
Using a cut-off based on the 95th percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over-expressed in 48% of patients with stage I cancer, 55% of patients with stage II cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31% patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients with early stage cancer that were negative for CA125. The combination of B7-H4 and CA125 identified 56 early stage cancer patients (65%) as positive. Correlation of marker expression to clinical outcome showed that high B7-H4 levels were correlated with poor prognosis. However, the effect was not significant when outcome was adjusted for other clinicopathological variables.
B7-H4 expression was low in normal ovaries and in benign tumors while half of early stage and two-thirds of late stage cancers over-expressed B7-H4. The data are consistent with previous observations and support further investigation of B7-H4 in the detection of early stage ovarian cancer either alone, or in combination with CA125.
本研究对新型生物标志物B7-H4在卵巢癌组织、正常卵巢组织及卵巢良性肿瘤中的表达进行特征分析，并评估其与CA125的关系。
采用酶联免疫吸附测定（ELISA）法检测251例卵巢癌患者卵巢组织裂解物中B7-H4和CA125的水平。作为对照，检测了43例卵巢良性肿瘤患者和32例正常卵巢患者的卵巢组织。将标志物浓度与CA125表达、临床病理变量及患者预后进行关联分析。
以对照组中B7-H4或CA125浓度的第95百分位数为临界值，I期癌症患者中48%、II期癌症患者中55%以及晚期癌症患者中67%的B7-H4呈过表达。早期癌症患者中31%的CA125升高。30例CA125阴性的早期癌症患者的肿瘤中B7-H4升高。B7-H4和CA125联合检测可将56例（65%）早期癌症患者判定为阳性。标志物表达与临床预后的相关性分析显示，高B7-H4水平与预后不良相关。然而，在对其他临床病理变量进行校正后，该效应并不显著。
正常卵巢组织和良性肿瘤中B7-H4表达较低，而半数早期癌症和三分之二的晚期癌症中B7-H4呈过表达。这些数据与之前的观察结果一致，支持进一步研究B7-H4在早期卵巢癌检测中单独应用或与CA125联合应用的价值。
