Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective

Abstract

Ovarian cancer (OC) represents the most lethal gynecological cancer and the poor prognosis is often attributable to late diagnosis. The diagnostic approach to woman presenting with pelvic mass is difficult and differential diagnosis often requires invasive histological examination. Serum CA125 and HE4, as well as the most of the other serum biomarkers discovered and validated, are not sufficiently sensitive and specific to make early diagnosis. Moreover, conflicting results exist about the improvement of diagnostic performance by using multivariate index assays, developed by combining circulating biomarkers with other variables (i.e., ultrasound and/or menopausal status and/or age), in comparison to CA125 or HE4 alone. In the last years, several studies focused on the microRNAs (miRs), short single-stranded non-coding RNA that regulate several messenger RNAs (mRNAs). As in other cancer types, the aberrant miRs expression has been demonstrated in gynecological cancers, in both tissues and serum samples. In particular, the diagnostic performance of single or miRs panels resulted very high. However, to date, despite the potential clinical utility has been demonstrated, none of these miRs has been validated in large OC populations.

Relative Ratios Enhance the Diagnostic Power of Phospholipids in Distinguishing Benign and Cancerous Ovarian Masses

“…Factors such as differences in age, gender, comorbid metabolic diseases, diet, and fasting status can significantly impact serum levels of metabolites and proteins [26,27]. Furthermore, metabolomics is particularly susceptible to degradation during sample processing [5]. However, previous research has demonstrated that phospholipids are less impacted by variability in diet and, with the exception of LPA, are stable and resistant to degeneration during processing and storage [9].…”

“…Methods pursued thus far include proteomics, metabolomics, and lipidomics. However, the vast majority of recent research has investigated proteomics-based approaches [5]. While CA-125 and other protein-based biomarkers have demonstrated the most success detecting ovarian cancer thus far, recent studies have found that implementation of CA-125 in ovarian cancer screening protocols have not made an equivocal impact on patient survival.…”

Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types

“…A feasible way to diagnose cancer at an early stage is to establish a useful and comprehensive diagnostic biomarker. To date, only 2 biomarkers, cancer antigen 125 (CA125) and human epididymis 4 (HE4) have been approved by the Food and Drug Administration as biomarkers for EOC [ 5 ]. Several studies have reported that HE4 has the highest sensitivity for detecting EOC as a single biomarker; while a combined biomarker of CA125 and HE4 is a more accurate predictor of malignancy than either alone [ 6 – 8 ].…”

The Diagnostic Accuracy of Human Epididymis Factor 4 for the Prediction of Optimal Debulking in Patients With Ovarian Cancer: A Meta-Analysis of Observational Studies

“…2,3 Optimal debulking surgery in combination with adjuvant chemotherapy is considered the criterion standard for the treatment of advanced ovarian cancer. 4 Suboptimal debulking surgery is related to poor prognosis, and the decision to perform primary versus secondary debulking relies on the extent of the disease and the surgeon's experience.…”