Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, characterized by continuous mucosal inflammation. Recently, some studies have considered it as part of an inflammatory bowel disease-based global network. Herein, with the aim of identifying the underlying potential genetic mechanisms involved in the development of UC, multiple algorithms for weighted correlation network analysis (WGCNA), principal component analysis (PCA), and linear models for microarray data algorithm (LIMMA) were used to identify the hub genes. The map of platelet activation, ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway showed significant links with UC development, and the hub genes CCR7, CXCL10, CXCL9, IDO1, MMP9, and VCAM1, which are associated with immune dysregulation and tumorigenesis in biological function, were found by multiple powerful bioinformatics methods. Analysis of The Cancer Genome Atlas (TCGA) also showed that the low expression of CCR7, CXCL10, CXCL9, and MMP9 may be correlated with a poor prognosis of overall survival (OS) in colorectal cancer (CRC) patients (all p < 0.05), while no significance detected in both of IDO1 and VCAM1. In addition, low expression of CCR7, CXCL10, CXCL9, MMP9, and IDO1 may be associated with a poor prognosis in recurrence free survival (RFS) time (all p < 0.05), but no significant difference was identified in VCAM1. Moreover, the NFKB1, FLI1, and STAT1 with the highest enrichment score were detected as the master regulators of hub genes. In summary, these results indicated the central role of the hub genes of CCR7, CXCL10, CXCL9, IDO1, VCAM1, and MMP9, in response to UC progression, as well as the development of UC to CRC, thus shedding light on the molecular mechanisms involved and assisting with drug target validation.

Background: Lipid metabolism-related genes (LMRGs) have been reported to be correlated with the immune infiltration of colorectal cancer (CRC). This study aimed to investigate the immune infiltration characteristics along the colorectal adenoma-carcinoma sequence (ACS) based on LMRGs. Methods: Gene expression data of colorectal adenoma and carcinoma samples were obtained from the public databases. The “limma” package was applied to determine the differentially expressed LMRGs. Unsupervised consensus clustering was used to cluster colorectal samples. The features of the tumor microenvironment were analyzed by the “ESTIMATE”, “GSVA”, and “TIDE” algorithms. Results: The expression of 149 differentially expressed LMRGs was defined as the LMRG signature. Based on this signature, the adenoma and carcinoma samples were divided into three clusters. Unexpectedly, these sequential clusters showed a directional relationship and collectively constituted the progressive course of colorectal ACS. Interestingly, the LMRG signature revealed that adenoma progression was accompanied by a progressive loss of immune infiltration and a stepwise establishment of a cold microenvironment, but carcinoma progression was characterized by a progressive gain of immune infiltration and a gradual establishment of a hot microenvironment. Conclusions: The LMRG signature reveals dynamic immune infiltration along the colorectal ACS, which substantially changes the understanding of the tumor microenvironment of CRC carcinogenesis and provides novel insight into the role of lipid metabolism in this process.

The prevalence of fundic gland polyps (FGPs) is increasing. Some researchers consider this increase to be associated strongly with the long-term use of proton-pump inhibitors (PPIs); however, not all researchers share this belief. There are minimal data on the development of FGPs in China. Therefore, we aimed to investigate the prevalence of FGPs and risk factors associated with the development of this disease. We studied 10 904 consecutive patients who underwent gastroduodenal endoscopies at our digestive endoscopy center between February 2011 and January 2013. Information on sex, age, Helicobacter pylori infection, PPIs intake, and the pathological results of the polyps were collected in the FGPs group and in the control group. The use of PPIs, sex, and H. pylori infection were statistically evaluated as dichotomous variables using a χ-test; age was evaluated as a continuous variable using a t-test. Finally, these factors were evaluated using a multiple logistic regression analysis. Gastric polyps were found in 759 (7.0%) patients, and 213 (2.0%) of these patients had FGPs. FGPs accounted for 28.1% of the gastric polyps. In the FGPs group, the percentage of H. pylori infection was 66.8% and the percentage of PPIs intake for at least 12 months was 23.1%. In the control group, the percentage of H. pylori infection was 77.4% and the percentage of PPIs intake for at least 12 months was 2.3%. The difference in the long-term use of PPIs was statistically significant between these two groups [χ=33.98, P<0.05, odds ratio (OR)=12.83, 95% confidence interval (CI): 4.47-36.80]. The results of the logistic regression were as follows: long-term use of PPIs (P<0.01, OR=14.11, 95% CI: 4.15-47.93); age (P<0.01, OR=1.69, 95% CI: 1.31-2.18). The P-values for sex and H. pylori infection were higher than 0.05. Age and the long-term use of PPIs were risk factors for the presence of FGPs; the long-term use of PPIs was a particularly strong risk factor.

There is no consensus on the effect of the probiotics on postoperative adaptive immunity in patients undergoing surgical resection for CRC. We aimed to systematically evaluate the effect of probiotics on postoperative adaptive immunity in perioperative CRC patients. The main end points were postoperative serum IgG, IgA, IgM, CD4⁺ T-cells, CD8⁺ T-cells and CD4⁺-to-CD8⁺ ratio. Meta-analysis was performed with a fixed or random effects model. We included six randomized controlled trials (RCTs) with 492 perioperative CRC patients. The use of enteral probiotics significantly increased the levels of peripheral blood IgG (MD: 1.33; 95% CI: 0.88 − 1.77; I² = 41%), IgA (MD: 0.20; 95% CI: 0.10 − 0.30; I² = 53%), IgM (MD: 0.18; 95% CI: 0.13 − 0.24; I² = 41%), CD4⁺ T-cells (MD: 2.79; 95% CI: 2.34 − 3.24; I² = 0) and CD4⁺-to-CD8⁺ ratio (MD: 0.09; 95% CI: 0.04 − 0.13; I² = 7%). In conclusion, we report that the use of enteral probiotics improves postoperative humoral and cellular immunity in patients with CRC.

INPLASY202160011 Pre-/probiotics improves postoperative adaptive immunity in colorectal cancer patients: a systematic review and meta-analysis Keywords: pre-/probiotics; colorectal cancer; adaptive immunity; perioperative period; meta-analysis. Download PDF – 202160011 Review Status: Ongoing