Endometrial cancer (EC) is the most frequent gynecologic cancer in postmenopausal women. Pathogenetic mechanisms that are related to the onset and progression of the disease are largely still unknown. A multi-omics strategy can help identify altered pathways that could be targeted for improving therapeutical approaches. In this study we used a multi-omics approach on four EC cell lines for the identification of common dysregulated pathways in type 1 and 2 ECs. We analyzed proteomics and metabolomics of AN3CA, HEC1A, KLE and ISHIKAWA cell lines by mass spectrometry. The bioinformatic analysis identified 22 common pathways that are in common with both types of EC. In addition, we identified five proteins and 13 metabolites common to both types of EC. Western blotting analysis on 10 patients with type 1 and type 2 EC and 10 endometria samples confirmed the altered abundance of NPEPPS. Our multi-omics analysis identified dysregulated proteins and metabolites involved in EC tumor growth. Further studies are needed to understand the role of these molecules in EC. Our data can shed light on common pathways to better understand the mechanisms involved in the development and growth of EC, especially for the development of new therapies.

Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions—data-dependent acquisition (DDA) and data-independent acquisition (DIA)—on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.

Early detection of recurrences in gynecological cancers is crucial for women’s health. Circulating tumor DNA (ctDNA) analysis through liquid biopsy offers a promising approach for monitoring disease progression and identifying relapses. This study investigated the utility of digital Polymerase Chain Reaction (dPCR) for ctDNA detection in three gynecological cancer patients with clinically confirmed relapses during a two-year post-surgical follow-up. Patient-specific tumor mutations were identified through whole-exome sequencing (WES) and confirmed via Sanger sequencing. dPCR probes targeting these mutations were used to quantify the ctDNA levels in plasma samples collected throughout the follow-up period, and the findings were compared with standard serum biochemical markers. In two patients, persistent positive dPCR signals for the selected mutations were detected after tumor removal, with ctDNA levels progressively increasing even after post-surgical chemotherapy. Notably, dPCR identified elevated ctDNA levels before an increase in the cancer antigen 125 (CA125) biochemical marker was observed. In the third patient, no ctDNA signals from the two selected mutations were detected despite clinical evidence of recurrence, suggesting the emergence of new mutations. While this study highlights the promise of dPCR for early recurrence detection in gynecological cancers, it also underscores the critical need for comprehensive mutation panels to overcome the inherent challenges posed by tumor heterogeneity and the emergence of new mutations during disease progression.

Recent evidence has highlighted the role of the gut–brain axis in the progression of autism spectrum disorder (ASD), with significant changes in the gut microbiome of individuals with this condition. This report investigates the effects of probiotics and human milk oligosaccharide (HMO) supplements on the gut microbiome, inflammatory cytokine profile, and clinical outcomes in an ASD adolescent with chronic gastrointestinal dysfunction and cognitive impairment. Following treatment, we observed a decrease in proinflammatory cytokines’ concentration alongside Sutterella relative abundance, a bacterium reported to be linked with gastrointestinal diseases. Also, we reported a notable increase in mood stability. The study aims to evaluate the use of gut microbiome-based therapy in selected ASD patients, highlighting its potential to improve related clinical symptoms.

Background/Objectives: Endometrial cancer (EC) is the second most frequent gynecological malignant tumor in postmenopausal women. Pathogenic mechanisms related to the onset and development of the disease are still unknown. To identify dysregulated proteins associated with EC we exploited a combined in vitro/in silico approach analyzing the proteome of exosomes with advanced MS techniques and annotating their results by using Chymeris1 AI tools. Methods: To this aim in this pilot study, we performed a deep proteomics analysis with high resolution MS (HRMS), advanced computational tools and western blotting for proteomics data validation. Results: That allowed us to identify 3628 proteins in serum albumin-depleted exosomes from 10 patients with EC compared to 10 healthy controls. This is the largest number of proteins identified in EC serum EVs. After quantification and statistical analysis, we identified 373 significantly (p < 0.05) dysregulated proteins involved in neutrophil and platelet degranulation pathways. A more detailed bioinformatics analysis revealed 61 dysregulated enzymes related to metabolic and catabolic pathways linked to tumor invasion. Through this analysis, we identified 49 metabolic and catabolic pathways related to tumor growth. Conclusions: Altogether, data shed light on the metabolic pathways involved in tumors. This is very important for understanding the metabolism of EC and for the development of new therapies.

Tonsils are secondary lymphoid organs that play a crucial role in the immunological response, with B cells being a major component involved in both innate and adaptive immunity. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and obstructive sleep apnea syndrome (OSAS) are both common pediatric conditions involving tonsillar pathology. In both syndromes, the molecular pathways dysregulated in tonsillar B cells are still to be understood. The study aimed to unravel and compare the proteomic profiles of tonsillar CD19+ B cells isolated from pediatric patients with PFAPA (n = 6) and OSAS (n = 6) to identify disease-specific molecular signatures. B cells were isolated from the tonsillar tissue using magnetic microbeads (with a purity of 93.50%). Proteomic analysis was performed by nanoLC-MS/MS with both data-dependent (DDA) and data-independent acquisition (DIA) methods, followed by comprehensive bioinformatic analysis. By merging DDA and DIA datasets, a total of 18.078 unique proteins were identified. Differential expression analysis revealed 83 proteins increased and 49 proteins decreased in OSAS B cells compared to PFAPA B cells (fold change ≥ 1.5 or ≤0.6, p < 0.05). Distinct pathway enrichments were highlighted, including alterations in the regulation of PTEN gene transcription, circadian gene expression, inflammasome pathways (IPAF and AIM2), and the metabolism of angiotensinogen to angiotensin. Specific proteins such as p53, Hdac3, RPTOR, MED1, Caspase-1, Cathepsin D, Chymase, and TLR2 (validated by WB) were shown to be differentially expressed. These findings reveal distinct proteomic signatures in tonsillar B cells from patients with PFAPA and OSAS, offering novel insights into the pathophysiology and potential avenues for biomarker discovery.