Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer

作者：Clarke Charlotte H^*; Yip Christine; Badgwell Donna; Fung Eric T; Coombes Kevin R; Zhang Zhen; Lu Karen H; Bast Robert C Jr

来源：Gynecologic Oncology, 2011, 122(3): 548-553.

DOI：10.1016/j.ygyno.2011.06.002

• Ovarian cancer
• CA125
• Early detection
• Biomarker

Objective. The low prevalence of ovarian cancer demands both high sensitivity (> 75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers.
Methods. Sera from 41 patients with early stage (I/II) and Si with late stage (III/IV) epithelial ovarian cancer. 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein At (Apo-Al). truncated transthyretin (TT), transferrin, hepcidin, ss-2-microglobulin (ss2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 ([T]H4)]. Statistical models were fit by logistic regression. followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls.
Results. In a training set analysis, the 3 most effective biomarkers (Apo-A1,TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA 125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P-0.015, McNemar's test).
Conclusion. Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer.

• 出版日期2011-9