Endometrial cancer belongs to the most common gynecologic cancer types globally, with increasing incidence. There are numerous ways of classifying different cases. The most recent decade has brought advances in molecular classification, which show more accurate prognostic factors and the possibility of personalised adjuvant treatment. In addition, diagnostic approaches lag behind these advances, with methods causing patients discomfort while lacking the reproducibility of tissue sampling for biopsy. Minimally invasive liquid biopsies could therefore represent an alternative screening and diagnostic approach in patients with endometrial cancer. The method could potentially detect molecular changes in this cancer type and identify patients at early stages. In this pilot study, we tested such a detection method based on circulating tumour DNA isolated from the peripheral blood plasma of 21 Slovak endometrial cancer patients. We successfully detected oncomutations in the circulating DNA of every single patient, although the prognostic value of the detected mutations failed to offer certainty. Furthermore, we detected changes associated with clonal hematopoiesis, including DNMT3A mutations, which were present in the majority of circulating tumour DNA samples.

This study investigated germline and somatic mutations in endometrial precancerous conditions and endometrial carcinoma to elucidate the molecular landscape of endometrial cancer development. Germline pathogenic variants were identified in 30.14% of endometrial precancerous cohort patients (n = 205). The most frequently altered genes in the endometrial precancerous cohort were CHEK2, SOS1, NBN, and SLX4. In the endometrial carcinoma cohort (n = 39), 20.51% of patients had germline PVs. Somatic mutation analysis of endometrial tumor tissues revealed frequent variants in PTEN, PIK3CA, ARID1A, and TP53. Notably, the mean age of patients with germline pathogenic variants did not significantly differ from those without, in either cohort. We observed a higher prevalence of hereditary breast and ovarian cancer-associated PVs compared to Lynch syndrome-associated pathogenic variants in the endometrial precancerous cohort. Our findings underscore the importance of comprehensive genetic testing in individuals with endometrial precancerous lesions and contribute to a deeper understanding of the genetic factors influencing endometrial carcinoma development.

Endometrial cancer is a significant public health concern with rising incidence rates globally. Understanding the molecular mechanisms underlying this disease is crucial for developing effective therapeutic strategies. Our study aimed to characterize transcriptional changes in endometrial cancer tissues compared to adjusted healthy tissue. Using RNA sequencing, we identified 2483 differentially expressed genes (DEGs), including protein-coding genes, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). Notably, several known cancer-related genes were differentially expressed, such as MYC, AKT3, CCND1, and CDKN2A. Pathway analysis revealed significant alterations in cell cycle regulation, several signaling pathways, and metabolic processes. These findings provide valuable insights into the molecular pathways dysregulated in endometrial cancer. Our results may contribute to the development of novel therapeutic targets and biomarkers for this disease.