TY - JOUR
T1 - Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer
AU - Young Han, Chae
AU - Bedia, Jacob S.
AU - Yang, Wei Lei
AU - Hawley, Sarah J.
AU - Bergan, Lindsay
AU - Hopper, Marika
AU - Celestino, Joseph
AU - Guo, Jing
AU - Gornet, Terrie G.
AU - Soosaipillai, Antoninus
AU - Yang, Hailing
AU - Doskocil, Samantha D.
AU - Lokshin, Anna E.
AU - Handy, Beverly C.
AU - Diamandis, Eleftherios P.
AU - Moore, Richard G.
AU - Lu, Karen H.
AU - Lu, Zhen
AU - Anderson, Karen S.
AU - Drescher, Charles W.
AU - Skates, Steven J.
AU - Bast, Robert C.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/23
Y1 - 2024/3/23
N2 - Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. Conclusion: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.
AB - Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. Conclusion: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.
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U2 - 10.1038/s41416-023-02560-z
DO - 10.1038/s41416-023-02560-z
M3 - Article
C2 - 38195887
AN - SCOPUS:85181876398
SN - 0007-0920
VL - 130
SP - 861
EP - 868
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -