Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset

Early detection of ovarian cancer through screening may have impact on mortality from the disease. Approaches based on CA125 cut-off have not been effective. Longitudinal algorithms such as the Risk of Ovarian Cancer Algorithm (ROCA) to interpret CA125 have been shown to have higher sensitivity and specificity than a single cut-off. The aim of this study was to investigate whether other ovarian cancer-related biomarkers, Human Epididymis 4 (HE4), glycodelin, mesothelin, matrix metalloproteinase 7 (MMP7), and cytokeratin 19 fragment (CYFRA 21-1), could improve the performance of CA125 in detecting ovarian cancer earlier. Serum samples (single and serial) predating diagnosis from 47 women taking part in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) who went on to develop primary invasive ovarian, fallopian tube, or peritoneal cancer (index cancer) (170 samples) and 179 matched controls (893 samples) were included in the study. A multiplex immunobased assay platform (Becton Dickinson) allowing simultaneous measurement of the six serum markers was used. The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin) was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection.

[1]  Matthew Burnell,et al.  Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) , 2009, Journal of Family Planning and Reproductive Health Care.

[2]  D. Pauler,et al.  Screening Based on the Risk of Cancer Calculation From Bayesian Hierarchical Changepoint and Mixture Models of Longitudinal Markers , 2001 .

[3]  Qin He,et al.  Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. , 2008, Gynecologic oncology.

[4]  Charles W Drescher,et al.  Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. , 2010, Gynecologic oncology.

[5]  P Stieber,et al.  Significance of the tumour markers CA 125 II, CA 72-4, CASA and CYFRA 21-1 in ovarian carcinoma. , 1994, Anticancer research.

[6]  Giuseppe Lippi,et al.  The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? , 2011, Clinical chemistry and laboratory medicine.

[7]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[8]  Jacques Ferlay,et al.  GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012 , 2013 .

[9]  Volker Briese,et al.  Measurement of glycodelin A in fluids of benign ovarian cysts, borderline tumours and malignant ovarian cancer. , 2005, Anticancer research.

[10]  Nasrin GhasemiSamira HE4 combined with CA125: favorable screening tool for ovarian cancer , 2014 .

[11]  Charles W Drescher,et al.  Potential role of HE4 in multimodal screening for epithelial ovarian cancer. , 2011, Journal of the National Cancer Institute.

[12]  Holly Janes,et al.  Pivotal Evaluation of the Accuracy of a Biomarker Used for Classification or Prediction: Standards for Study Design , 2008, Journal of the National Cancer Institute.

[13]  J. Gohagan,et al.  Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. , 2011, JAMA.

[14]  Steven J Skates,et al.  A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. , 2009, Gynecologic oncology.

[15]  Michèl Schummer,et al.  The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. , 2003, Cancer research.

[16]  Timothy R Church,et al.  Results From Four Rounds of Ovarian Cancer Screening in a Randomized Trial , 2009, Obstetrics and gynecology.

[17]  I. Christensen,et al.  Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass. , 2012, Gynecologic oncology.

[18]  D. Goldstein,et al.  No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. , 2011, Gynecologic oncology.

[19]  Gary Goodman,et al.  Assessing Lead Time of Selected Ovarian Cancer Biomarkers: A Nested Case–Control Study , 2010, Journal of the National Cancer Institute.

[20]  Sudhir Srivastava,et al.  Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens , 2011, Cancer Prevention Research.

[21]  N Urban,et al.  Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma. , 2004, Gynecologic oncology.

[22]  Josef Chovanec,et al.  A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer - An international multicenter study in women with an ovarian mass. , 2015, Gynecologic oncology.

[23]  D Timmerman,et al.  HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm , 2011, British Journal of Cancer.