Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer.
The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 +/- 0.046 and 0.784 +/- 0.049, respectively, mean +/- SE) but were both significantly less than the AUC for CA125 (0.934 +/- 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 +/- 0.010) was significantly greater than that of CA125 alone (0.934 +/- 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women.
HealthLinx Ltd, Richmond, Victoria, Australia. g.rice@healthlinx.com.au
Gregory E
GE
Rice
Tracey A
TA
Edgell
Dominic J
DJ
Autelitano
D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000473:pathology; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D016889:Endometrial Neoplasms / Q000097:blood / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D000078792:Midkine; D009088:Mucoproteins; D015513:Oncogene Proteins; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012189:Retrospective Studies
C502296:AGR2 protein, human; D018394:CA-125 Antigen; D016207:Cytokines; C451759:MUC16 protein, human; D008565:Membrane Proteins; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D000078792:Midkine