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Communication Dans Un Congrès Année : 2021

Aptamers as diagnostic tools for the detection of Human Epididymis protein 4 (HE4), clinical biomarker of ovarian cancer

Résumé

Ovarian cancer is the most deadly gynecological cancer and eight leading cause of cancer-related deaths among women globally. When it is diagnosed in early stages, 5-year survival is approximately 90 %. However, due to the silent nature of the disease and lack of sensitive diagnostic methods, the majority of the patients are diagnosed in advances stages, with a 5-year survival of only 15 – 40 %. Unfortunately, there are no early-stage or screening methods available, so late diagnosis remains the main factor contributing to the high mortality. Recently, aptamers with affinity to molecular tumor biomarkers have emerged as useful diagnostic tools. Aptamers are non-coding, synthetic single-stranded DNA or RNA oligonucleotides that bind with high-affinity to the wide range of ligands, including cancer proteins. Similar as antibodies, they form unique secondary and tertiary structures that enable them recognition of the target. Due to their characteristics of high specificity, low toxicity, complete development in vitro and easy and reproducible synthesis, they could offer advantages over antibodies. Herein, we present a discovery method for high-affinity DNA aptamer sequences targeting Human Epididymis protein 4 (HE4). Human Epididymis protein 4 (HE4) is a protein overexpressed in ovarian cancer, but not in benign gynecological conditions or healthy individuals. Elevated HE4 levels are found in the blood and urine of ovarian cancer patients. Therefore, HE4 has an important role as clinical biomarker in the management of ovarian cancer. HE4 is currently used in the differential diagnosis of women with pelvic masses, prognosis and follow-up of ovarian cancer patients. The high-affinity single-stranded anti-HE4 DNA aptamers are selected from random, highly diverse DNA library using High-Fidelity Systematic Evolution of Ligands by EXponential enrichment (HI-FI SELEX) method. This diagnostic aptamer discovery method utilize sequence amplification by sensitive digital droplet Polymerase Chain Reaction (ddPCR). The selected anti-HE4 sequences and structures are identified using bioinformatics analysis. Described DNA aptamers will be further characterized, in order to be potentially used as molecular probes in the development of aptamer-based diagnostic methods, biosensors or Point-of-care testing (POCT) devices for ovarian cancer.
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Dates et versions

hal-03440770 , version 1 (03-12-2021)

Identifiants

  • HAL Id : hal-03440770 , version 1

Citer

Antonija Hanzek, Christian Siatka, Anne-Cécile E. Duc. Aptamers as diagnostic tools for the detection of Human Epididymis protein 4 (HE4), clinical biomarker of ovarian cancer. 17èmes Journées du Cancéropôle Grand Sud-Ouest, Cancéropôle Grand Sud-Ouest (GSO), Nov 2021, Carcassonne, France. ⟨hal-03440770⟩

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