Análise do perfil proteômico e metabolômico de tecidos com lesões precursoras do câncer de colo de útero em mulheres do Amazonas

Abstract

Cancer is one of the diseases with high mortality in the world. Among the most diagnosed cancers in women in Brazil, especially in the Amazonas, cervical cancer stands out. This type of cancer is usually preceded by precursor lesions known as grade 1, 2 and 3 cervical intraepithelial neoplasia (CIN), where the stages 2 and 3 are considered high grade. In order to prevent the progression of these precursor lesions to cancer cells, a better understanding of the process of CIN evolution is needed, as well as search new methods capable of identifying and diagnosing them. Currently, the use of proteomic and metabolomic approaches has been growing in the area of cancer research, allowing the investigation of possible alterations or/and interactions of proteins and metabolites due to a pathology. In this sense, the present study aims to analyze the proteomic and metabolomic profile of tissues with high-grade CIN, obtained from volunteer women at the Oncology Control Foundation Center of the Amazonas state (FCECON). For this, samples of tissues with high-grade lesions and their respective adjacent margins were collected and submitted to proteomic and metabolomic analysis. In proteomics, the shotgun proteomic approach was used to infer the protein profile with label-free quantitation by extracted ion chromatograms (XICs). In metabolomics, multivariate statistical analyzes such as PCA and PLS-DA were employed as well as the Random Forest approach to verify the differential metabolites present in these samples. As a result, it was verified in the proteomic analysis that each type of tissue has differences, presenting proteins abundant in each condition and overexpressed proteins correlated to cervical cancer. Some examples were cortactin, mucin-5B, calnexin and cofilin-1, which may be related to the persistence or molecular progression of these precursor lesions. In the metabolomic analysis, it was observed changes in the metabolite profiles between the tissues of CIN 2 and CIN 3 and their respective adjacent margins, being consistent with the data obtained in proteomics. In addition, it was noted the presence of some metabolites that can contribute to the distinction of these tissues such as histamine, present mainly in the margins adjacent to the precursor lesions of the CCU. Therefore, the data found in this work demonstrate interesting features which we hope to contribute to a broader molecular understanding of the possible mechanisms of progression in such cells studied.