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Molecular Signatures of High-Grade Cervical Lesions.

Frontiers in oncology | 2018

Cervical cancer is the fourth most common neoplasia in women and the infection with human papilloma virus (HPV) is its necessary cause. Screening methods, currently based on cytology and HPV DNA tests, display low specificity/sensitivity, reducing the efficacy of cervical cancer screening programs. Herein, molecular signatures of cervical cytologic specimens revealed by liquid chromatography-mass spectrometry (LC-MS), were tested in their ability to provide a metabolomic screening for cervical cancer. These molecules were tested whether they could clinically differentiate insignificant HPV infections from precancerous lesions. For that, high-grade squamous intraepithelial lesions (HSIL)-related metabolites were compared to those of no cervical lesions in women with and without HPV infection. Samples were collected from women diagnosed with normal cervix (N = 40) and from those detected with HSIL from cytology and colposcopy (N = 40). Liquid-based cytology diagnosis, DNA HPV-detection test, and LC-MS analysis were carried out for all the samples. The same sample, in a customized collection medium, could be used for all the diagnostic techniques employed here. The metabolomic profile of cervical cancer provided by LC-MS was found to indicate unique molecular signatures for HSIL, being two ceramides and a sphingosine metabolite. These molecules occurred independently of women's HPV status and could be related to the pre-neoplastic phenotype. Statistical models based on such findings could correctly discriminate and classify HSIL and no cervical lesion women. The results showcase the potential of LC-MS as an emerging technology for clinical use in cervical cancer screening, although further validation with a larger sample set is still necessary.

Pubmed ID: 29707519 RIS Download

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A multi-institutional effort to identify and quantitate, using a systems biology approach and sophisticated mass spectrometers, all of the major - and many minor - lipid species in mammalian cells, as well as to quantitate the changes in these species in response to perturbation. The goal of their research is to better understand lipid metabolism and the active role lipids play in diabetes, stroke, cancer, arthritis, Alzheimer's and other lipid-based diseases in order to facilitate development of more effective treatments. Resources available include: LIPID MAPS publications, detailed biochemical pathways, improved protocols for lipid separation and quantification, analytical tools for determining lipid quantitation, structure drawing tools for automatically drawing lipid molecular structures in stereochemical detail, and experimental data. The LIPID MAPS organization includes six lipidomics core laboratories, each specialized in extracting, identifying, and quantifying one of the major categories of mammalian lipids: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and prenol lipids. Other core laboratories and bridge projects include bioinformatics, mass spectrometric imaging, lipid synthesis, oxidized lipids, and macrophage biology and genomics.

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RRID:SCR_015538

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RRID:SCR_015539

Web server for statistical, functional and integrative analysis of metabolomics data. Web based tool suite used for metabolomic data processing, normalization, multivariate statistical analysis, and data annotation, biomarker discovery and classification.

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RRID:SCR_010500

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