Background: Witches’ broom disease (WBD) of cacao (Theobroma cacaoL.), caused byMoniliophthora perniciosa, is the most important limiting factor for the cacao production in Brazil. Hence, the development of cacao genotypes with durable resistance is the key challenge for control the disease. Proteomic methods are often used to study the interactions between hosts and pathogens, therefore helping classical plant breeding projects on the development of resistant genotypes. The present study compared the proteomic alterations between two cacao genotypes standard for WBD resistance and susceptibility, in response toM. perniciosainfection at 72 h and 45 days post-inoculation; respectively the very early stages of the biotrophic and necrotrophic stages of the cacao xM. perniciosainteraction.Results: A total of 554 proteins were identified, being 246 in the susceptible Catongo and 308 in the resistant TSH1188 genotypes. The identified proteins were involved mainly in metabolism, energy, defense and oxidative stress. The resistant genotype showed more expressed proteins with more variability associated with stress and defense, while the susceptible genotype exhibited more repressed proteins. Among these proteins, stand out pathogenesis related proteins (PRs), oxidative stress regulation related proteins, and trypsin inhibitors. Interaction networks were predicted, and a complex protein-protein interaction was observed. Some proteins showed a high number of interactions, suggesting that those proteins may function as cross-talkers between these biological functions.Conclusions: We present the first study reporting the proteomic alterations of resistant and susceptible genotypes in theT. cacaoxM. perniciosapathosystem. The important altered proteins identified in the present study are related to key biologic functions in resistance, such as oxidative stress, especially in the resistant genotype TSH1188, that showed a strong mechanism of detoxification. Also, the positive regulation of defense and stress proteins were more evident in this genotype. Proteins with significant roles against fungal plant pathogens, such as chitinases, trypsin inhibitors and PR 5 were also identified, and they may be good resistance markers. Finally, important biological functions, such as stress and defense, photosynthesis, oxidative stress and carbohydrate metabolism were differentially impacted withM. perniciosainfection in each genotype.

Among the many challenges in cancer diagnosis is the early distinction between metastatic cancer and a secondary tumor. This difficulty stems from the lack of markers that offer high sensitivity and specificity and can be easily applied in routine laboratory work. An example of this challenge is distinguishing gastric metastases originating from breast cancer from a gastric primary tumor. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of this study was to analyze the expression of HNF4A, estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein 15 (GCDFP-15) in a Brazilian cohort. We performed immunohistochemistry analysis of HNF4A, ER, PR and GCDFP-15 in 126 patients divided into three cohorts: primary breast cancer, primary gastric cancer and both types of tumors. Our data confirmed the sensitivity and specificity of the HNF4A marker compared to other currently used clinical markers. HNF4A alone could be a gold standard marker for distinguishing primary gastric cancer from breast metastasis, thus validating its potential clinical use, especially in populations with high genetic diversity.

Breast cancer treatment has advanced enormously in the last decade. Most of this is due to advances reached in the knowledge regarding tumor biology, mainly in the field of diagnosis and treatment....

Breast cancer (BC) has been extensively studied, as it is one of the more commonly diagnosed cancer types worldwide. The study of miRNAs has increased what is known about the complexity of pathways and signaling and has identified potential biomarkers and therapeutic targets. Thus, miRNome profiling could provide important information regarding the molecular mechanisms involved in BC. On average, more than 430 miRNAs were identified as differentially expressed between BC cell lines and normal breast HMEC cells. From these, 110 miRNAs were common to BC subtypes. The miRNome enrichment analysis and interaction maps highlighted epigenetic-related pathways shared by all BC cell lines and revealed potential miRNA targets. Quantitative evaluation of BC patient samples and GETx/TCGA-BRCA datasets confirmed MYB and EZH2 as potential targets from BC miRNome. Moreover, overall survival was impacted by EZH2 expression. The expression of 15 miRNAs, selected according to aggressiveness of BC subtypes, was confirmed in TCGA-BRCA dataset. Of these miRNAs, miRNA-mRNA interaction prediction revealed 7 novel or underexplored miRNAs in BC: miR-1271-5p, miR-130a-5p, and miR-134 as MYB regulators and miR-138-5p, miR-455-3p, miR-487a, and miR-487b as EZH2 regulators. Herein, we report a novel molecular miRNA signature for BC and identify potential miRNA/mRNAs involved in disease subtypes.

Background/Objectives: Despite its heterogeneity and diagnostic challenges, acute myeloid leukemia (AML) originates from stem cell transformation and alterations in the hematopoietic niche (HN) could be related to leukemic transformation. Therefore, the aim of this study was to evaluate the protein profile of HN from AML patients and compare it with the profile of healthy donors (HDs). Methods: A proteomic analysis was conducted to identify differentially expressed (DE) proteins in BM plasma from AML patients and HD. In silico analysis was performed to identify biological processes and signaling pathways involved. Additionally, ELISA confirmed the expression of the DE protein of interest in BM plasma samples. Results: Proteomic analysis revealed alterations in the plasma profiles of AML patients and 36 DE proteins were found. Among then, we highlight C8G, CFB, SAA1, SERPINA3 and SERPINC1, which are related to inflammatory response process. Thus, considering the role of the secreted protein SAA1 in the inflammatory context and that it is described as a potential biomarker in several tumors, we selected SAA1 for ELISA confirmation. The results corroborated our findings, indicating that increased expression of SAA1 could be related to AML. Our results also revealed that SAA1 can stimulate immune signaling through NF-kappa-B activation. Conclusions: These findings position SAA1 as a promising biomarker for AML diagnosis, offering a potential tool for more accurate identification of the disease. Nevertheless, further studies are needed to understand the relationship of SAA1 with the leukemic transformation process in AML and its potential clinical use.