TY - JOUR
T1 - Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers
AU - Bahar-Shany, Keren
AU - Barnabas, Georgina D.
AU - Deutsch, Lisa
AU - Deutsch, Netanel
AU - Glick-Saar, Efrat
AU - Dominissini, Dan
AU - Sapoznik, Stav
AU - Helpman, Limor
AU - Perri, Tamar
AU - Blecher, Anna
AU - Katz, Guy
AU - Yagel, Itai
AU - Rosenblatt, Orgad
AU - Shai, Daniel
AU - Brandt, Benny
AU - Meyer, Raanan
AU - Mohr-Sasson, Aya
AU - Volodarsky-Perel, Alexander
AU - Zilberman, Itamar
AU - Armon, Shunit
AU - Jakobson-Setton, Ariella
AU - Eitan, Ram
AU - Kadan, Yfat
AU - Beiner, Mario
AU - Josephy, Dana
AU - Brodsky, Malka
AU - Friedman, Eitan
AU - Anafi, Liat
AU - Molchanov, Yossef
AU - Korach, Jacob
AU - Geiger, Tamar
AU - Levanon, Keren
N1 - Publisher Copyright:
© 2022 UICC.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.
AB - No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.
KW - BRCA
KW - early detection biomarker
KW - ovarian cancer
KW - utero-tubal lavage
UR - http://www.scopus.com/inward/record.url?scp=85140207532&partnerID=8YFLogxK
U2 - 10.1002/ijc.34318
DO - 10.1002/ijc.34318
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C2 - 36214786
AN - SCOPUS:85140207532
SN - 0020-7136
VL - 152
SP - 781
EP - 793
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -