Colorectal cancer (CRC) is the third most common cancer worldwide. The high mortality from CRC is mainly related to metastasis affecting distant organs and their function. Dissemination of tumor cells from the primary tumor and hematogeneous spread are considered crucial in the formation of tumor metastases. The analysis of circulating tumor cells (CTCs) and CTC clusters in the blood can be used for the early detection of invasive cancer. Moreover, CTCs have a prognostic significance in the monitoring of a malignant disease or the response to chemotherapy. This work presents an overview of the research conducted on CTCs with the aim of finding suitable detection systems and assessing the possibility of clinical applications in patients with CRC.

Ovarian cancer is the deadliest gynecological cancer. With non-specific symptoms of the disease and the lack of effective diagnostic methods, late diagnosis remains the crucial hurdle of the poor prognosis. Therefore, development of novel diagnostic approaches are needed. The purpose of this study is to develop DNA-based aptamers as potential diagnostic probes to detect ovarian cancer biomarker Human epididymis protein 4 (HE4) in urine. HE4 is a protein overexpressed in ovarian cancer, but not in healthy or benign conditions. With high stability and diagnostic value for detection of ovarian cancer, urine HE4 appears as an attractive non-invasive biomarker. The high-affinity anti-HE4 DNA aptamers were selected through 10 cycles of High Fidelity Systematic Evolution of Ligands by EXponential enrichment (Hi-Fi SELEX), a method for aptamer selection based on digital droplet PCR. The anti-HE4 aptamers were identified using DNA sequencing and bioinformatics analysis. The candidate aptamer probes were characterized in urine for binding to HE4 protein using thermofluorimetry. Two anti-HE4 aptamers, AHE1 and AHE3, displayed binding to HE4 protein in urine, with a constant of dissociation in the nanomolar range, with K_d (AHE1) = 87 ± 9 nM and K_d (AHE3) aptamer of 127 ± 28 nM. Therefore, these aptamers could be promising tools for application in diagnostics and future development of urine tests or biosensors for ovarian cancer.

Diagnostic role of urine human epididymis protein 4 in ovarian cancer

Le cancer de l'ovaire est le cancer gynécologique le plus mortel dans le monde. La détection précoce est la clé pour la plupart des cancers, mais pour le cancer de l'ovaire, le diagnostic tardif reste l'un des principaux obstacles au rétablissement et à la survie des patientes avec un taux de mortalité très élevé. À l'heure actuelle, il n'existe pas de test de diagnostic spécifique et suffisamment sensible pour la maladie à un stade précoce. L'objectif du projet CARIBOU (CAncer ovaRIan BiosensOr in Urine) est le développement d'aptamères d'acides nucléiques de haute spécificité pour la détection de biomarqueurs du cancer dans l'urine. La nouvelle méthode utilisée pour obtenir la partie détection du biocapteur, High-Fidelity Systematic Evolution of Ligands by EXponential enrichment (Hi-Fi SELEX), est utilisée pour la sélection d'aptamères qui ciblent spécifiquement et avec sensibilité les biomarqueurs. Les biomarqueurs du cancer présents dans l'urine sont stables, permettant une détection facile et homogène. A terme, l'utilisation des aptamères comme outils de diagnostic en biocapteur permettrait de développer un test non-invasif pour une utilisation systématique en première ligne.