Screening of Prognostic Factors in Early-Onset Breast Cancer
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
Authors: Yu, Zhun; He, Qi; Xu, Guoping
Abstract
Background: Gene expression profiles from early-onset breast cancer and normal tissues were analyzed to explore the genes and prognostic factors associated with breast cancer. Methods: GSE109169 and GSE89116 were obtained from the database of Gene Expression Omnibus. We firstly screened the differentially expressed genes between tumor samples and normal samples from patients with early-onset breast cancer. Based on database for annotation, visualization and intergrated discovery (DAVID) tool, functional analysis was calculated. Transcription factor-target regulation and microRNA-target gene network were constructed using the tool of transcriptional regulatory relatitionships unraveled by sentence-based text mining (TRRUST) and miRWalk2.0, respectively. The prognosis-related survival information was compiled based on The Cancer Genome Atlas breast cancer clinical data. Results: A total of 708 differentially expressed genes from GSE109169 data sets and 358 differentially expressed genes from GSE89116 data sets were obtained, of which 122 common differentially expressed genes including 102 uniformly downregulated genes and 20 uniformly upregulated genes were screened. Protein-protein interaction network with a total of 83 nodes and 157 relationship pairs was obtained, and genes in protein-protein interaction, such as peroxisome proliferator-activated receptor gamma, FGF2, adiponectin, and PCK1, were recognized as key nodes in protein-protein interaction. In total, 66 transcription factor-target relationship pairs were obtained, and peroxisome proliferator-activated receptor gamma was the only one downregulated transcription factor. MicroRNA-target gene network contained 368 microRNA-target relationship pairs. Moreover, 16 differentially expressed genes, including 2 upregulations and 14 downregulations, were related to a significant correlation with the prognosis, including SQLE and peroxisome proliferator-activated receptor gamma. Conclusions: SQLE and peroxisome proliferator-activated receptor gamma might be important prognostic factors in breast cancers, and adiponectin might be important in breast cancer pathogenesis regulated by peroxisome proliferator-activated receptor gamma.
Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells
CLINICAL NUTRITION
Authors: Beisani, Marc; Pappa, Stella; Moreno, Pau; Martinez, Eva; Tarasco, Jordi; Luisa Granada, Maria; Puig, Rocio; Cremades, Manel; Puig-Domingo, Manel; Jorda, Mireia; Pellitero, Silvia; Balibrea, Jose M.
Abstract
Background & aims: Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. Methods: From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. Results: Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylationidemethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. Conclusions: FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.