TY - JOUR
T1 - Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer
AU - Clarke, Charlotte H.
AU - Yip, Christine
AU - Badgwell, Donna
AU - Fung, Eric T.
AU - Coombes, Kevin R.
AU - Zhang, Zhen
AU - Lu, Karen H.
AU - Bast, Robert C.
N1 - Funding Information:
This work was supported by funds from the M.D. Anderson SPORE in Ovarian Cancer NCI P50 CA83639 , the Bioinformatics Shared Resources of the M.D. Anderson CCSG NCI P30 CA16672 and philanthropic support from Golfers Against Cancer , the Tracey Jo Wilson Foundation and the Mossy Foundation .
PY - 2011/9
Y1 - 2011/9
N2 - 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 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. 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, CA125 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.
AB - 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 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. 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, CA125 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.
KW - Biomarker
KW - CA125
KW - Early detection
KW - Ovarian cancer
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U2 - 10.1016/j.ygyno.2011.06.002
DO - 10.1016/j.ygyno.2011.06.002
M3 - Article
C2 - 21708402
AN - SCOPUS:80051545198
SN - 0090-8258
VL - 122
SP - 548
EP - 553
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -