Concomitant dysregulation of the estrogen receptor and BRAF/MEK signaling pathways is common in colorectal cancer and predicts a worse prognosis

AbstractPurposeRecurrence is a major cause of colorectal cancer (CRC)-related death. As yet, the accurate identification of CRC patients at high risk of recurrence is still a major clinical challenge. Previously, we found that an estrogen receptor (ER) pathway gene signature may predict disease recurrence in CRC patients. The aim of this study is to evaluate the potential application of additional pathway-specific gene signatures in the prediction of CRC recurrence.MethodsThe activities of 26 cancer-related pathways in CRC were semi-quantified using gene signature-based Bayesian binary regression analysis, and putative associations of the pathways with cancer recurrence risk were assessed using survival analysis.ResultsAmong the 26 pathways tested, inactivation of the estrogen receptor (ER) pathway was found to be one of the most common events in CRC. Inactivation of this pathway was found to be frequently accompanied by over-activation of the BRAF/MEK pathway, and these two pathways were found to be associated with opposite effects on several clinicopathological CRC features, including microsatellite instability, subsite location, advanced stage and recurrence. Survival analysis of four independent CRC patient cohorts revealed that while the BRAF/MEK pathway was more strongly associated with recurrence than the ER pathway in mixed-stage CRCs, the ER pathway was a better predictor of recurrence than the BRAF/MEK pathway in stage II CRC. A combined use of these two pathways im...
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research

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In conclusion, the molecular and functional analysis of circulating tumor cells and circulating nucleic acids can be used as companion diagnostics to improve the stratification of therapies and to obtain insights into therapy-induced selection of cancer cells.. PMID: 31833325 [PubMed - as supplied by publisher]
Source: Journal of Biological Regulators and Homeostatic Agents - Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research
This study documents the antioxidative, anticancer and enzyme-inhibiting properties of potential probiotic Bacillus strains isolated from fermented brine mango pickle. Antioxidant activity was determined through in-vitro assays namely, DPPH•, ABTS•+, hydroxyl radical scavenging ability, reducing activity, superoxide anion scavenging ability, linoleic acid and plasma lipid peroxidation ability. Both intact cells (IC) and intracellular cell-free extracts (CFE) from most of the strains exhibited prominent antioxidant activity. Likewise, CFE and intracellular cell-free supernatants (CFS) exhibited potential inhibitor...
Source: Food Chemistry - Category: Food Science Source Type: research
Conclusion: According to these data, monitoring this class of toxicities is of primary importance to avoid hypertension worsening and, thus, the risk of major cardiovascular events. PMID: 31829045 [PubMed - as supplied by publisher]
Source: Expert Review of Cardiovascular Therapy - Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
Abstract Comparison and detection of stable cancer genes across cancer types is of interest. The gene expression data of 6 different cancer types (colon, breast, lung, ovarian, brain and renal) and a control group from The Cancer Genome Atlas (TCGA) database were used in this study. The comparison of gene expression data together with the calculation standard deviations of such data was completed using a statistical model for the detection of stable genes. Genes having similar expression (referred as flexible genes) pattern to the control group in four out of six cancer types are PATE, NEUROD4 and TRAFD1. Moreover...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Epigenomics, Ahead of Print.
Source: Future Medicine: Epigenomics - Category: Genetics & Stem Cells Authors: Source Type: research
Authors: Lappalainen J, Holmström D, Lepistö A, Saarnio J, Mecklin JP, Seppälä T Abstract Background: Lifetime incidence of colorectal cancer (CRC) especially in carriers of MLH1 and MSH2 pathogenic germline variants in mismatch repair genes is high despite ongoing colonoscopy surveillance. Lynch syndrome (LS) registries have been criticized for not reporting colonoscopy quality adequately.Methods: Prospective follow-up data from the national registry were combined with a retrospective assessment of the colonoscopy reports from Helsinki University Hospital electronic patients records in 2004-201...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Conclusion: We confirmed the distinct STING expression in CRC and demonstrated its independent prognostic value in survival outcomes. STING could be a potential therapeutic target that enhances anti-cancer immune response in CRC.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
RBP7 is a member of the cellular retinol-binding protein (CRBP) family and previous data suggested a link between CRBPs and the malignant transformation of colon cancer cells. Here, we investigated the potential of RBP7 as a predictive biomarker for patients with colon cancer and determined its functional relevance for tumor progression. We analyzed RBP7 protein and mRNA expression in independent tissue collections of colon cancers with recorded follow-up data, including data from TCGA. We used gene set enrichment analyses to characterize its functional role. Effects of RBP7 on migration and invasion were determined in tra...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Unresolved inflammation, due to insufficient production of proresolving anti-inflammatory lipid mediators, can lead to tumorigenesis. Among these mediators, lipoxin A4 (LXA4) has potent anti-carcinogenic properties, and may serve as key target for modulating inflammation-associated cancer like colorectal cancer. The purpose of present study was to clarify the roles of LXA4 in colorectal cancer. We investigated the effects and underlying mechanisms of LXA4 in colorectal cancer and its relationship with tumor-associated inflammation and immune microenvironment by employing clinical samples and mouse colorectal cancer cell li...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
The objective of this study is to prospectively determine the association between gastric polyps and colorectal neoplasia.Methods A multicenter prospective cross-sectional study was performed from July 2012 to December 2014. We compared patients with and without gastric polyps for prevalence of colorectal adenomas. The odds ratios (OR) were computed by logistic regression analysis after multivariable adjustments.Results Totally 1546 patients were included, with 770 patients in the gastric polyp group and 776 in the age- and sex- matched control group. Patients with gastric polyps had greater odds of having any colorectal a...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
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