Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening.

In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10-15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE) mode (UPLC-QTOF-MSE) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients' plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.

A Retrospective Analysis of Colorectal Serrated Lesions from 2005 to 2014 in a Single Center: Importance of the Establishment of Diagnostic Patterns.

BACKGROUND: Serrated colorectal lesions are increasingly recognized as an important process in the development of colorectal cancer. Endoscopic and histological diagnosis may be difficult, and knowledge of the serrated lesions is important for the establishment of strategies for treating colorectal lesions. We aimed to analyze serrated lesions diagnosed at a single center and evaluate if there was an increase in their identification over the years. DESIGN AND SETTING: A retrospective analysis of colonoscopy reports was performed at a specialized center from 2005 to 2014. METHODS: Colonoscopy reports about any resected endoscopic lesions were reviewed and subjected to histological diagnosis from 2005 to 2014. Then, serrated lesions were evaluated based on morphological characterization, location, size, occurrence of synchronous lesions, and the patient's history of colorectal cancer and polyps. RESULTS: A total of 2126 colonoscopy examination reports were reviewed, and 3494 lesions were analyzed. On histopathological examination, 1089 (31.2%) were classified as hyperplastic polyps, 22 (0.6%) as sessile serrated adenomas, and 21 (0.6%) as traditional serrated adenomas. There was an increase in the number of cases of sessile and traditional serrated adenomas diagnosed after 2010. Before 2010, two cases of sessile serrated adenomas and seven cases of traditional serrated adenomas were diagnosed; after 2010, 20 cases of sessile serrated adenoma and 14 cases of traditional serrated adenomas were diagnosed. CONCLUSION: There was an increase in the diagnosis of sessile serrated adenomas over the years, which can be attributed to better accuracy in colonoscopy and histological classification.

Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.

It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.

The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR-RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner.

Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis.

It was investigated whether dietary polyunsaturated fatty acids (PUFA) could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO) and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C), fish (F) or a mixture of fish and soybean oil (SF). The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-gamma), MPO and DNA damage. The disease activity index (DAI) was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-gamma and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.

Analysis of oxidative DNA damage in patients with colorectal cancer.

PURPOSE: The aim of this study was to measure the levels of oxidative DNA damage in cells isolated from the colon mucosa in patients with colorectal cancer and to compare normal and neoplastic tissues and make correlations with anatomopathologic variables. PATIENTS AND METHODS: Thirty-three patients with colorectal adenocarcinoma were studied. The oxidative DNA damage was evaluated by means of the alkaline version of the comet assay. RESULTS: For all the patients studied, it was found that the cells obtained from the neoplastic tissue presented oxidative DNA damage greater than in the cells from normal tissue. The cells isolated from the neoplastic mucosal tissue of the colon presented significantly greater mean extent of DNA strand breakage than the cells isolated from normal tissue. Additionally, the patients at earlier stages of the Dukes and TNM classifications presented higher levels of oxidative damage than those at more advanced stages. CONCLUSION: Assessment of the levels of oxidative damage at the different stages of colorectal carcinogenesis is of great interest because it enables evaluation of the effectiveness of antioxidant substances that could be used as preventive measures against the initial oxidative aggressive action on the colonic mucosa.