RNA biomarkers from proximal liquid biopsy for diagnosis of ovarian cancer

BACKGROUND: Most ovarian cancer patients are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers that are sensitive for early stage disease are lacking. This medical need justifies the search for novel approaches using utero-tubal lavage as a proximal liquid biopsy. METHODS: In this study, we explore the extracellular transcriptome of utero-tubal lavage fluid obtained from 26 ovarian cancer patients and 48 controls using messenger RNA (mRNA) capture and small RNA sequencing. RESULTS: We observed an enrichment of ovarian and fallopian tube specific messenger RNAs in utero-tubal lavage fluid compared to other human biofluids. Over 300 mRNAs and 41 miRNAs were upregulated in ovarian cancer samples compared with controls. Upregulated genes were enriched for genes involved in cell cycle activation and proliferation, hinting at a tumor-derived signal. CONCLUSION: This is a proof-of-principle that mRNA capture sequencing of utero-tubal lavage fluid is technically feasible, and that the extracellular transcriptome of utero-tubal lavage should be further explored in larger cohorts to assess the diagnostic value of the biomarkers identified in this study. IMPACT: Proximal liquid biopsy from the gynecologic tract is a promising source for mRNA and miRNA biomarkers for diagnosis of early-stage ovarian cancer.