TY - JOUR
T1 - Validation of a novel biomarker panel for the detection of ovarian cancer
AU - Leung, Felix
AU - Bernardini, Marcus Q.
AU - Brown, Marshall D.
AU - Zheng, Yingye
AU - Molina, Rafael
AU - Bast, Robert C.
AU - Davis, Gerard
AU - Serra, Stefano
AU - Diamandis, Eleftherios P.
AU - Kulasingam, Vathany
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/9
Y1 - 2016/9
N2 - Background: Ovarian cancer is the most lethal gynecological malignancy. Our integrated-omics approach to ovarian cancer biomarker discovery has identified kallikrein 6 (KLK6) and folatereceptor 1 (FOLR1) as promising candidates but these markers require further validation. Methods: KLK6, FOLR1, CA125, and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls, and 216 ovarian cancer patients. The serum biomarker levels were determined by ELISA or automated immunoassay. Results: All biomarkers demonstrated elevations in the sera of ovarian cancer patients compared with controls (P < 0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify ovarian cancer patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. In addition, the combination of HE4 and FOLR1 was a strong predictor of ovarian cancer diagnosis, displaying comparable sensitivity (65%) to the bestperforming CA125-based models (67%) at a set specificity of 95%. Conclusions: The markers identified through our integrated-omics approach performed similarly to the clinically approved markers CA125 and HE4. Furthermore, HE4represents a powerful diagnostic marker for ovarian cancer and should be used more routinely in a clinical setting. Impact: The implications of our study are 2-fold: (i) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (ii) we have demonstrated the clinical utility of our integrated-omics approach to identifying novel serum markers with comparable performance to clinical markers.
AB - Background: Ovarian cancer is the most lethal gynecological malignancy. Our integrated-omics approach to ovarian cancer biomarker discovery has identified kallikrein 6 (KLK6) and folatereceptor 1 (FOLR1) as promising candidates but these markers require further validation. Methods: KLK6, FOLR1, CA125, and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls, and 216 ovarian cancer patients. The serum biomarker levels were determined by ELISA or automated immunoassay. Results: All biomarkers demonstrated elevations in the sera of ovarian cancer patients compared with controls (P < 0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify ovarian cancer patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. In addition, the combination of HE4 and FOLR1 was a strong predictor of ovarian cancer diagnosis, displaying comparable sensitivity (65%) to the bestperforming CA125-based models (67%) at a set specificity of 95%. Conclusions: The markers identified through our integrated-omics approach performed similarly to the clinically approved markers CA125 and HE4. Furthermore, HE4represents a powerful diagnostic marker for ovarian cancer and should be used more routinely in a clinical setting. Impact: The implications of our study are 2-fold: (i) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (ii) we have demonstrated the clinical utility of our integrated-omics approach to identifying novel serum markers with comparable performance to clinical markers.
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U2 - 10.1158/1055-9965.EPI-15-1299
DO - 10.1158/1055-9965.EPI-15-1299
M3 - Review article
C2 - 27448593
AN - SCOPUS:84986206618
SN - 1055-9965
VL - 25
SP - 1333
EP - 1340
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 9
ER -