Diagnostic Value and Clinical Significance of Methylated SEPT9 for Colorectal Cancer: A Meta-Analysis.

BACKGROUND This meta-analysis aimed to clarify the diagnostic role of plasma methylated SEPT9 (mSEPT9) in colorectal cancer (CRC) and examined its association with CRC. MATERIAL AND METHODS A systematic review was conducted prior to July 2018. Summary sensitivity, specificity, and positive and negative likelihood ratio (PLR/NLR) were calculated for the diagnostic value of mSEPT9 for CRC. The areas under the receiver operating curves (AUCs) were used to summarize the overall test performance. RESULTS Twenty-two studies with 2271 CRC patients were enrolled. The summary sensitivity, specificity, PLR, NLR, DOR, and AUC of the overall analysis of mSEPT9 were 0.69, 0.92, 8.1, 0.34, 24, and 0.89, respectively. Subgroup and meta-regression analyses demonstrated that the diagnostic value was higher for the Epi proColon 2.0 assay, Asian ethnicity, and mSEPT9 test combined with fecal occult blood test (FOBT) or fecal immunochemical test (FIT) than for other test methods, white ethnicity, and mSEPT9 test alone. The rate of mSEPT9 positivity was higher in advanced CRC cases compared with early-stage CRC cases, and was higher in CRC cases than in adenoma cases. No significant difference in mSEPT9 positivity rate was found between left- and right-sided CRC. CONCLUSIONS Plasma mSEPT9 has a high diagnostic value for CRC, especially on the newly developed Epi proColon test 2.0 method. The diagnostic sensitivity is superior among Asians compared to whites, and the combination of mSEPT9 and FOBT/FIT has a better performance than mSEPT9 alone. Finally, the expression of mSEPT9 is associated with CRC stage but not with location.

Bioinformatics analysis of genomic and immune infiltration patterns in autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a specific type of pervasive developmental disorder, and most studies suggest that the onset of autism may be related to genetic and immune factors. The etiology of autism and the underlying molecular events need to be further addressed. Methods: The ASD-related dataset GSE18123 was downloaded from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to screen for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that may be associated with autism. The top 5,000 genes with an absolute median difference were obtained, and a co-expression network was constructed using weighted correlation network analysis (WGCNA). In addition, GO and KEGG enrichment analyses were performed for genes in the modules most closely related to ASD. Hub genes were found in the significant modules, and the expression values and receiver operating characteristic (ROC) curves of the hub genes were analyzed and validated. Immune cell infiltration in ASD was calculated using the CIBERSORT algorithm, and the relationship between hub genes and immune cells was analyzed. Finally, GSEA was used to explore the potential pathways of hub genes affecting ASD. Results: The 5,000 DEGs were divided into eight significant modules by WGCNA. The green module was most significantly associated with ASD, and two hub genes [fatty acid-binding protein 2 (FABP2) and Janus kinase 2 (JAK2)] were found. Immune cell infiltration showed that resting dendritic cells and monocytes differed significantly in ASD and healthy individuals. FABP2 was significantly associated with memory B cells and CD8 T cells. JAK2 was significantly associated with monocytes, CD4 activated memory T cells, CD4 resting memory T cells, activated dendritic cells, gamma delta T cells, regulatory T cells (Tregs), CD8 T cells, and naïve CD4 T cells. FABP2 and JAK2 were found to affect multiple pathways of immunity. Conclusions: FABP2 and JAK2 may influence the immune microenvironment of ASD by regulating immune cells and immune-related pathways and are candidate molecular markers for the development of ASD.

miR-28-5p inhibits carcinogenesis in colon cancer cells and is necessary for erastin-induced ferroptosis.

BACKGROUND: Ferroptosis is a newly discovered type of regulated cell death, the underlying mechanisms of which need to be further illuminated. The regulatory activity of miR-28-5p in ferroptosis in colon cancer cells is currently unclear. This study set out to investigate the effect of miR-28-5p on ferroptosis in colon cancer cells and determine its underlying mechanism. METHODS: Biochemical Kits were used to measure iron concentration, malondialdehyde (MDA) concentration, glutathione (GSH) concentration and glutathione peroxidase (GPX) vitality. Cell counting kit 8 (CCK8) assays were conducted to evaluate cell viability. Flow cytometry was conducted to assess apoptosis. Transwell™ assays were used to measure the migratory and invasive abilities of HCT116 cells. Western blotting was used to measure the protein relative expression of NEDD4 binding protein 1 (N4BP1). Quantitative real-time polymerase chain reaction (RT-PCR) was used to measure the RNA relative expression of N4BP1 and miR-28-5p. RESULTS: Ferroptosis was induced in HCT116 cells by erastin in a dose- and time-dependent manner, which caused significant inhibition of proliferation, migration, and invasion in HCT116 cells; however, there was no obvious effect on apoptosis. miR-28-5p expression was decreased in colon cancer cells compared with the normal colon cells but was upregulated in erastin-treated HTC116 cells. Additionally, when overexpressed via the transfection of miR-28-5p mimics, miR-28-5p had an inhibitive effect on proliferation, migration, and invasion, while promoting apoptosis, in HCT116 cells. erastin-induced ferroptosis was also increased by miR-28-5p overexpression. Compared with normal colon cells, following erastin treatment, NEDD4 binding protein 1 (N4BP1) expression was increased in colon cancer cells and further decreased in HTC116 cells. miR-28-5p overexpression also inhibited N4BP1 mRNA and protein expression in HTC116 cells. CONCLUSIONS: miR-28-5p plays an important role in ferroptosis by targeting N4BP1 and could serve as a potential therapeutic approach for colon cancer.

Genome-wide analysis to identify a novel distant metastasis-related gene signature predicting survival in patients with gastric cancer.

This study designed to identify a potential novel distant metastasis-related gene (DMGs) signature that predicting prognosis in patients with gastric cancer. DMGs was screened by overlapping the differentially expressed genes between M0 and M1 stage, and between tumor and adjacent normal tissue of gastric cancer by analyzing The Cancer Genome Atlas (TCGA) dataset. There were 83 DMGs were identified, the integrative analysis revealed these DMGs were involved in several biological process and pathway. A six-DMGs prognostic signature was developed based on the risk score obtained from Cox analysis. Patients with low risk score presented significantly shorter survival time. This prognostic signature has a moderate predictive value for the overall survival in gastric cancer patients, with an area under curve of 0.604. The DMGs prognostic signature also significantly associated with the overall survival of gastric cancer patients, and showed a better performance for predicting prognosis than traditional clinical indicators. The joint effect of risk score with clinical features could remarkably increased the predictive value as compared with single variable. The results from 60 gastric cancer tissues verified the prognostic value of the six-DMGs prognostic signature. In conclusions, the present study identified a novel six-DMGs prognostic signature that could serve as a biomarker for the prognosis prediction of patients with gastric cancer.