title: Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  LRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.
authors: University of Michigan, Department of Surgery, Ann Arbor, MI, United States of America.
authors: Jing
authors: J
authors: Wu
authors: University of Michigan, Department of Surgery, Ann Arbor, MI, United States of America.
authors: Haidi
authors: H
authors: Yin
authors: University of Michigan, Department of Surgery, Ann Arbor, MI, United States of America.
authors: Jianhui
authors: J
authors: Zhu
authors: University of Michigan, Department of Internal Medicine, Ann Arbor, MI, United States of America.
authors: Ronald J
authors: RJ
authors: Buckanovich
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Jason D
authors: JD
authors: Thorpe
authors: University of Texas MD Anderson Cancer Center, Biostatistics, Houston, TX, United States of America.
authors: Jianliang
authors: J
authors: Dai
authors: Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Nicole
authors: N
authors: Urban
authors: University of Michigan, Department of Surgery, Ann Arbor, MI, United States of America.
authors: David M
authors: DM
authors: Lubman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D006023:Glycoproteins; C015246:LRG1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins