A Clinical Diagnostic Value Analysis of Serum CA125, CA199, and HE4 in Women with Early Ovarian Cancer: Systematic Review and Meta-Analysis

Abstract

Objective. To evaluate the value of combined detection of serum CA125, CA199, and HE4 in the diagnosis of ovarian cancer. Methods. Relevant articles retrieved from PubMed, Elsevier Science, Springer, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were screened strictly according to inclusion and exclusion criteria. Included literature published from January 2005 to December 2021. (2) Serum HE4, CA125, CA199, and their combination for ovarian cancer diagnostic tests were studied, and healthy subjects or patients with the benign disease were taken as a control group. (3) Pathological tissue diagnosis as the gold standard. (4) Complete original data can be obtained. (5) The sample size was ≥20. (6) Language is limited to Chinese and English. Data features and QUADAS table were extracted from the included literature, and QUADAS evaluation tool detail table was used for the included study. Conduct quality evaluation. Statistical analysis was carried out using meta-disc software version 1.4. Appropriate effect model was selected to merge the effect size, and the forest maps of merge sensitivity, merge specificity, and merge likelihood ratio were obtained. Results. The results of meta-analysis showed that there was a statistical difference in diagnostic specificity analysis of CA125 ( OR = 1.91 , 95% CI (1.58, 2.32), P < 0.00001 , I 2 = 67 % , Z = 6.58 ); diagnostic sensitivity analysis of CA125 ( OR = 2.50 , 95% CI (1.73, 3.62), P < 0.00001 , I 2 = 0 % , Z = 4.90 ); diagnostic specificity analysis of CA199 ( OR = 1.98 , 95% CI (1.60, 2.44), P < 0.00001 , I 2 = 89 % , Z = 6.35 ); diagnostic sensitivity analysis of CA199 ( OR = 1.92 , 95% CI (1.46, 2.52), P < 0.00001 , I 2 = 73 % , Z = 4.70 ); diagnostic specificity analysis of HE4 ( OR = 2.08 , 95% CI (1.65, 2.63), P < 0.00001 , I 2 = 73 % , Z = 6.19 ); diagnostic sensitivity analysis of HE4 ( OR = 2.37 , 95% CI (1.87, 3.00), P < 0.00001 , I 2 = 83 % , Z = 7.19 ). Conclusion. In the clinical assisted diagnosis of ovarian cancer, combined detection of CA125, CA199, and HE4 has the stronger discriminant ability and higher accuracy than single detection of CA125, which can improve the diagnostic efficiency.

Molecular Biomarkers for the Early Detection of Ovarian Cancer

“…This leads to a decrease in the PPV; the results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial indicated that the PPV for CA125 alone was only 3.7% [ 21 ]. The performance of CA125 varies in different cancer tissue types, with a poor performance in non-epithelial ovarian cancers, clear cell carcinomas, undifferentiated carcinomas, and mucinous carcinomas [ 22 ]. Many other factors can influence serum CA125 levels, leading to variations in the baseline CA125 levels in different women.…”

Ovarian Cancer Diagnosis and Prognosis Based on Cell-Free DNA Methylation

“…Additional tumor markers like CA199 and CEA may also show elevated levels but lack specificity to OC, often associated with gastrointestinal malignancies. 4 While imaging can be used to detect ovarian masses, it cannot make a definitive diagnosis or differentiate benign from malignant lesions, and the lesion cannot be detected until the size reaches a significant level. 5 There remains a deficiency in specificity concerning tumor marker testing alone, transvaginal ultrasound screening alone, or their combined use, which results in unsatisfactory rates of early detection.…”

Circulating tumor cells help differentiate benign ovarian lesions from cancer before surgery: A literature review and proof of concept study using flow cytometry with fluorescence imaging

“…The use of blood biomarkers for monitoring cancer status or recurrence, carcinoembryonic antigen (CEA) ( 10 ), carbohydrate antigen 19-9 ( 11 ), human epididymis secretory protein 4 ( 11 ), apolipoprotein A1 ( 12 ), transthyretin ( 13 ), transferrin ( 14 ) and β2-macroglobulin ( 15 ), is well documented. Although these markers could facilitate earlier detection of recurrence, their utility is limited by inadequate sensitivity or specificity ( 16 , 17 ).…”