Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis

SIMPLE SUMMARY: Abnormal uterine bleeding (AUB) is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women’s health, since all women presenting with bleeding will undergo sequential invasive tests, avoidable in 90–95% of those women who do not have EC. This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of EC diagnostic protein biomarkers. Samples collected with a Rovers Cervex Brush(®) and the HC2 DNA collection device, Digene, were the most suitable for EC proteomic studies. A clinical retrospective study assessing the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), by targeted proteomics, identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential EC protein biomarkers in cervical fluids (AUC > 0.8). This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients. ABSTRACT: Background: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women’s health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90–95% of those women who do not have EC. Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC. We evaluated the protein quantity and the proteome composition of five cervical sampling methods. Results: Samples collected with a Rovers Cervex Brush(®) and the HC2 DNA collection device, Digene, were the most suitable samples for EC proteomic studies. Most proteins found in uterine fluids were also detected in both cervical samples. We then conducted a clinical retrospective study to assess the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), using targeted proteomics. We identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential protein biomarkers to discriminate between EC and symptomatic non-EC women with abnormal uterine bleeding in cervical fluids (AUC > 0.8). Conclusions: This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients.