HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients

Abstract

Background To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. Methods This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). Results Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. Conclusions ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

Sensitivity and Specificity of Selected Biomarkers and Their Combinations in the Diagnosis of Ovarian Cancer

“…In addition, Dochez V. et al [26], who studied the usefulness of CA125, HE4, ROMA, and RMI tests in the diagnosis of ovarian cancer, showed that the most effective diagnostic method to date is the simultaneous determination of CA125 and HE4 [26]. Braicu EI et al [27] discovered that CA125, HE4, and ROMA exhibit markedly improved diagnostic performance in advanced ovarian cancer (AUC > 0.92) compared to early stage. The researchers found that in the differentiation between OC and endometriosis, both the ROMA (SN 99%) and HE4 (SN 98.1%) performed superiorly compared to CA125 (SN 75.0%) with a specificity rate of 75.4% [27].…”

Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer

“…Currently, the most commonly used tumor marker for OC screening in clinical practice is Carbohydrate Antigen 125 (CA125) [ 21 ] and Human Epididymis Protein 4 (HE4) [ 22 ]. Given that other benign diseases can also cause elevated serum biomarkers, the diagnostic specificity and sensitivity of using serum CA125 or HE4 alone are not high [ 23 ]. Existing studies have attempted to establish prognostic models for patients with OC based on clinicopathologic characteristics.…”

“…Existing studies have attempted to establish prognostic models for patients with OC based on clinicopathologic characteristics. For instance, the Risk of Ovarian Malignancy Algorithm (ROMA) model incorporated both serum CA125 and HE4, nevertheless, the model did not fully address the challenge of detecting OC with high risk [ 23 ].…”

Comparative Analysis of Gene Expression Analysis Methods for RNA In Situ Hybridization Images

“…WFDC2 is a well-established ovarian cancer biomarker (AlSomairi et al, 2024;Braicu et al, 2022;Utkarsh et al, 2023) and is also associated with HGSC patient survival (James et al, 2022). PPIB was selected as a control gene, and it is already used in several ovarian cancer studies by RNAscope assay and RT-PCR analysis (Desbois et al, 2020;Pan & Ma, 2020).…”

“…CCNE1 amplification, occurring in 15-20% of HGSC cases (Bell et al, 2011; Jamalzadeh et al, 2022; Marone et al, 1998), has been linked to HGSC patient survival (Chan et al, 2020; Jamalzadeh et al, 2022; Stronach et al, 2018). WFDC2 is a well-established ovarian cancer biomarker (AlSomairi et al, 2024; Braicu et al, 2022; Utkarsh et al, 2023) and is also associated with HGSC patient survival (James et al, 2022). PPIB was selected as a control gene, and it is already used in several ovarian cancer studies by RNAscope assay and RT-PCR analysis (Desbois et al, 2020; Pan & Ma, 2020).…”