Women’s Health and Early Diagnosis: Multi-Omics Liquid Biopsy for Gynecological Cancers.
Gynecological tumors, such as those of the ovary, uterus, and cervix, have a significant impact on women’s health. Early diagnosis is crucial: the five-year survival rate is 80-90% if detected early, compared to 15-25% in advanced stages. However, effective screening methods for the ovary and uterus are lacking, and there is currently no universal biomarker that covers all gynecological tumors. Liquid biopsy, which is minimally invasive, can identify multiple tumors simultaneously and represents a promising strategy for early diagnosis. The project integrates the analysis of circulating free DNA with peptidomics and lipidomics from blood in a “Transformer” AI, designed for natural language processing, which treats each type of omics as a different “language” and allows for capturing long-range relationships between different layers. The goal is to obtain a minimally invasive test with high sensitivity and specificity to support women’s health.
Soft Tissue Sarcomas
Soft Tissue Sarcomas (STSs) are rare cancers originating from mesenchymal tissues and are associated with high mortality despite improved survival rates. Accurate diagnosis is challenging, as over 40% of initial histological assessments change upon re-evaluation, potentially affecting treatment decisions. Our research aims to characterize the molecular signatures of primary STSs through genomic, proteomic, and metabolomic analyses of liquid biopsies to identify circulating biomarkers related to disease aggressiveness and phases. This approach seeks to enhance diagnostic accuracy and enable innovative, patient-specific therapies. Currently, nuclear magnetic resonance metabolomic profiling of serum samples is identifying small molecules as biomarkers for stratifying patients into STS subtypes and assessing disease progression.
Alkaptonuria
Alkaptonuria (AKU) is a rare metabolic disorder caused by the accumulation of homogentisic acid (HGA), resulting from variants in the homogentisate-1,2-dioxygenase (HGD) gene. This leads to reduced enzyme activity and the development of an ochronotic pigment. While research often targets the metabolic degradation of HGA via 4-hydroxyphenylpyruvate, our untargeted NMR investigation revealed a parallel decarboxylation route to 4-hydroxyphenylacetate, suggesting new biomarkers for AKU. We are also analyzing the chemical structure of the ochronotic pigment through nuclear magnetic resonance and mass spectrometry, aiming to identify intermediate species in the HGA transformation process to develop new therapies that disrupt pigment formation.