Protein biomarkers in gynecological cancers: The need for translational research towards clinical applications

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Ovarian cancer is ranked highest among gynecological cancers, followed by cervical and endometrial cancer. Most women are asymptomatic and are eventually diagnosed with late-stage disease. Numerous recent studies have proposed promising protein tumour biomarkers for diagnosis, prognosis, treatment and disease recurrence. Cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4) are biomarkers routinely used for monitoring recurrence in ovarian cancer patients. They are of limited diagnostic value in early-stage cancer. Application of sensitive advanced proteomics techniques reveals that a combined biomarker panel is superior in specificity and sensitivity compared to a single biomarker. The major limitation in translating potential tumour biomarkers from the research setting to clinical practice is a lack of validation in large patient cohorts. This review provides an overview of current and potential biomarkers for ovarian, endometrial and cervical cancers. In conclusion, we propose validation studies for multiple biomarker panels of apolipoprotein A-I (ApoA-I)+CA-125+transthyretin and vascular cell adhesion molecule-1 (VCAM-1)+CA-125+carcinoembryonic antigen (CEA)+HE4 for early diagnosis of ovarian cancer. We also suggest combination panels of prognostic value consisting of CA-125+HE4 for endometrial cancer and squamous cell carcinoma antigen (SCC-Ag)+CEA for cervical cancer.