Wu Jing, Yin Haidi, Zhu Jianhui, Buckanovich Ronald J, Thorpe Jason D, Dai Jianliang, Urban Nicole, Lubman David M
University of Michigan, Department of Surgery, Ann Arbor, MI, United States of America.
University of Michigan, Department of Internal Medicine, Ann Arbor, MI, United States of America.
PLoS One. 2015 Mar 23;10(3):e0121112. doi: 10.1371/journal.pone.0121112. eCollection 2015.
Leucine-rich alpha-2-glycoprotein (LRG1) was found to be differentially expressed in sera from patients with Epithelial Ovarian Cancer (EOC). The aim of this study is to investigate the performance of LRG1 for detection of EOC, including early stage EOC, and to evaluate if LRG1 can complement CA125 in order to improve EOC detection using two independent blinded sample sets.
Serum LRG1 and CA125 were measured by immunoassays. All assays were performed blinded to clinical data. Using the two independent sample sets (156 participants for sample set 1, and 233 for sample set 2), LRG1 was differentially expressed in EOC cases as compared to healthy, surgical, and benign controls, and its performance was not affected by the conditions of blood collection. The areas under the ROC curve (AUC) for LRG1 in differentiating EOC cases from non-cases were 0.797 and 0.786 for sample set 1 and 2. For differentiating EOC cases from healthy controls, the AUC values for LRG1 were 0.792 and 0.794. At a fixed specificity of 95%, LRG1 detects 52%, and 53.5% of EOC cases from healthy controls for sample set 1 and 2. When combining LRG1 and CA125, the AUC value increased to 0.927, which was improved compared to CA125 (AUC=0.916) (p=0.008) alone in distinguishing EOC cases from non-cases. More importantly, LRG1 also showed potential performance in differentiating early stage EOC from non-cases with an AUC of 0.715 for sample set 1, and 0.690 for sample set 2. The combination of LRG1 and CA125 resulted in an AUC of 0.838, which outperforms CA125 (AUC=0.785) (p=0.018) in detecting early stage EOC cases from non-cases using the larger sample set.
LRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.
富含亮氨酸的α-2-糖蛋白（LRG1）在上皮性卵巢癌（EOC）患者血清中存在差异表达。本研究旨在探究LRG1用于检测EOC（包括早期EOC）的性能，并评估LRG1能否与CA125互补，以利用两个独立的盲法样本集改善EOC检测。
采用免疫分析法检测血清LRG1和CA125。所有检测均对临床数据设盲。利用两个独立样本集（样本集1有156名参与者，样本集2有233名），与健康、手术及良性对照相比，LRG1在EOC病例中存在差异表达，且其性能不受采血条件影响。样本集1和2中，LRG1区分EOC病例与非病例的ROC曲线下面积（AUC）分别为0.797和0.786。对于区分EOC病例与健康对照，LRG1的AUC值分别为0.792和0.794。在固定特异性为95%时，样本集1和2中LRG1从健康对照中检测出52%和53.5%的EOC病例。当将LRG1与CA125联合使用时，区分EOC病例与非病例的AUC值增至0.927，相较于单独使用CA125（AUC = 0.916）（p = 0.008）有所提高。更重要的是，LRG1在区分早期EOC病例与非病例方面也显示出潜在性能，样本集1的AUC为0.715，样本集2的AUC为0.690。在使用较大样本集检测早期EOC病例与非病例时，LRG1与CA125联合使用的AUC为0.838，优于CA125（AUC = 0.785）（p = 0.018）。
LRG1单独或与CA125联合使用可能是诊断卵巢癌的有用生物标志物。
