Objective: Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and are implicated in the development of multiple cancers by blocking differentiation and promoting proliferation. However, little is known about the function of distinct CBX proteins in colorectal cancer. Methods: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of CBXs in colorectal cancer patients. Results: The expression levels of CBX1/2/3/4/5 and CBX8 were significantly elevated in CRC tissues, whereas the expression levels of CBX6/7 were reduced. CBX3 was significantly associated with the clinical cancer stage and short disease-free survival (DFS) in CRC patients. High mRNA expression of CBX5/6 was associated with short overall survival (OS) in rectal cancer patients. CBX3/5/6 could be potential prognostic biomarkers for the survival of CRC patients. Moreover, the functions of the differentially expressed CBXs were primarily related to the SUMOylation of DNA methylation proteins and chromatin organization and may regulate the pluripotency of stem cells. The expression of CBXs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in colon cancers and rectal cancers. Conclusions: Our study may provide novel insights for the selection of prognostic biomarkers of CBX family in colorectal cancer.
Gastric cancer (GC) is one of the most common malignancies, with an ever-increasing incidence and high mortality rate. Chromobox4 (CBX4), also named hPC2, is a small ubiquitin-related modifier (SUMO) E3 ligase. Previous studies have found that high CBX4 expression is associated with tumor size, pathologic differentiation and decreased patient survival in hepatocellular carcinoma (HCC). However, the expression and prognostic value of CBX4 in GC have not been clarified. In our study, ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioPortal, DAVID 6.8 and TIMER were utilized. RT-PCR, immunohistochemistry (IHC), Western blot, CCK-8 assay, cell apoptosis assay, cell cycle assay were used to further verify in GC tissue samples or cell line. The transcriptional and protein level of CBX4 in GC tissues was found significantly elevated and a significant association between the expression of CBX4 and clinicopathological parameters was found in GC patients. Low expression of CBX4 in GC patients were correlated with a significantly improved prognosis. The functions of CBX4 are primarily related to the stem cell pluripotency signaling pathway, Hippo signaling pathway, HTLV-I infection, Notch signaling pathway, and N-glycan biosynthesis. Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for GC.
Crohn’s disease (CD) is a chronic and relapsing inflammatory bowel disorder that has been shown to generate neurological impairments, which has the potential to signify disease activity in an underlying neurological manner. The objective of this study was to investigate the abnormalities of brain microstructure and the corresponding functional connectivity (FC) in patients with CD, as well as their associations with disease condition. Twenty-two patients with CD and 22 age-, gender-, and education-matched healthy controls (HCs) were enrolled in this study. All subjects underwent mean apparent propagator (MAP)-MRI and resting-state functional magnetic resonance imaging (MRI) (rs-fMRI) data collection. Each patient was evaluated clinically for the condition and duration of the disease. The MAP metrics were extracted and compared between two groups. Pearson’s correlation analysis was conducted to determine the relationship between disease characteristics and significantly abnormal MAP metrics in the CD group. Regions of interest (ROIs) for ROI-wise FC analysis were selected based on their correlation with MAP metrics. Results showed that multiple brain regions, including the parahippocampus and thalamus, exhibited statistically significant differences in MAP metrics between CD patients and HCs. Additionally, CD patients exhibited decreased FC between the left parahippocampus and bilateral thalamus, as well as the right parahippocampus and bilateral thalamus. The findings of this work provide preliminary evidence that structural abnormalities in the parahippocampal gyrus (PHG) and thalamus, as well as decreased FC between them, may reflect the degree of inflammatory of the disease and serve as brain biomarkers for evaluating CD activity.
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