Abnormal uterine bleeding is a common benign gynecologic complaint around the time of menopause, and is also the most common symptom of endometrial cancer. This complaint prompts in-office endometrial biopsy to exclude malignancy. Unfortunately, because only a limited portion of the lining tissue is sampled, the endometrial biopsy is not always accurate which can lead to delays in diagnosis and the potential for worsening of the disease and prognosis. Biomolecules have proven to be useful tools in cancer screening and early diagnosis. Liquid biopsy has been widely accepted as a less- or non-invasive way to obtain samples from patients, including blood, urine, saliva and other types of body fluids. However, no circulating biomarkers have been easily identified in the patient blood of endometrial cancer. MicroRNA are a class of small molecules and has shown promise in cancer detection. MicroRNAs may be detected in the biopsy tissue or by testing the fluid that cells secrete. Endometrial tissue is inherently difficult to sample in the office. Although direct sampling from the endometrium has limitations, but the fluid secreted by the lining endometrial epithelial cells can be easily sampled using a technique adapted from an in-office procedure known as a sonohysterography. This procedure is used in the evaluation of abnormal uterine bleeding by introducing saline solution into the endometrial cavity as a contrast material during transvaginal ultrasound. The infused saline is normally discarded, but can be collected for microRNA analysis. In this study, we report the preliminary results of potential miRNA biomarkers identified in 60 patient endometrial fluid collected using sonohystography technique. Patients were recruited who planned to undergo hysterectomy for either benign indication or for a known endometrial cancer diagnosis. The endometrial fluid was collected prior to surgery using a technique similar to that used in sonohysterography. The miRNA was extracted and quantitated. Following the reverse transcription, each sample was amplified on a customized microarray plate with known specific miRNA target primer printed in each well (miScrpt miRNA PCR Array). Patient demographic and health information was collected to be used in the final analysis along with the final pathology results of their surgery. In total, 60 patient samples have been collected and processed (30 cancer and 30 controls). Significant variations in expression were identified in several miRNA markers. Markers with at least a two-fold increase (e.g. miR-429, miR-146a-5p, miR-34b-3p) or decrease (e.g. miR-296-5p, miR-204-5p) in expression were considered candidates for validation. Twelve miRNA markers with the greatest variation in expression were chosen to be used on an additional set of patients to further validate the results. The results will be presented. The method developed here will provide a non-invasive way in early diagnosis and screening for endometrial cancer and therefore impact on improvement of women’s health.
Citation Format: Jianing Yang, Joel Barkley, Kameron Firouzi, Bikash Bhattarai, Dean Coonrod, Frederic Zenhausern. Identification and validation of endometrial cancer specific miRNA biomarkers in endometrial fluid collected using saline infused sonohysterography techniques [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO035.