Metabolomics and lipidomics in the differentiation of CIN 2 and CIN 3: an exploratory pilot study

Introduction High-grade cervical intraepithelial neoplasia (CIN 2–3) is a precursor lesion to cervical cancer and, although it presents different probabilities of regression and progression, it is usually grouped together in screening and managed similarly. However, the mechanisms that determine its evolution are still poorly understood, and standard treatment by conization can lead to reproductive complications such as subfertility and premature birth. Objective This study aimed to identify metabolic and lipid signatures that can distinguish between CIN 2 and CIN 3 lesions using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Methods Tissue samples from the lesion and adjacent margin of 24 women with CIN 2–3 were subjected to metabolomic and lipidomic analysis by LC-HRMS. Multivariate statistical analyses, pathway analysis, and correlation were performed to understand these neoplasms’ development and progression and identify potential metabolites and lipids to distinguish such lesions. Results Metabolomic and lipidomic analysis by LC-HRMS in cervical tissue identified molecular signatures with differential abundance between CIN 2 and CIN 3, highlighting patterns associated with the degree of lesion. Multivariate analyses highlighted metabolites (serine, glutamic acid, guanidine-6-monophosphate, succinic acid, mannose 6-phosphate, and taurine) and lipids (TG 49:1, TG 50:1, and TG 52:2) as the main contributors to the discrimination between the groups, suggesting relevant biological alterations in high-grade cervical lesions. Conclusion Combination metabolomic and lipidomic approach enabled the identification of metabolites and lipids potentially involved in the pathogenesis of intraepithelial neoplasia (CINs). In addition, these identified metabolite and lipid panels are promising as complementary tools for future screening strategies for these lesions.