ABSTRACT
Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer,analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers.Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications.Based on the distribution characteristics of H3K27ac,the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored.The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues.Compared with normal gastric mucosa,the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer.A total of 8847 enhancers with increased activity in intestinal type gastric cancer were identified,accounting for 8.3%of all enhancers,which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells.A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers,which was able to predict the overall survival of patients.Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer.These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC,E2F3 and other genes.A prognosis model based on enhancer target genes is constructed.
ABSTRACT
Objective To investigate the correlation of spinal mechanical imbalance and thoraco-dorsal pain of ankylosing spondylitis (AS). Methods The clinical data of 90 patients with AS were collected. Patients were divided into two groups according to the presence of thoracodorsal pain: the AS with thoraco-dorsal pain group (30 cases) and the AS without thoraco-dorsal pain group (60 cases). Clinical symptoms, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis measurement index (BASMI), ankylosing spondylitis disease activity (ASDAS), and spinal mechanical function and nuclear myocardial force test were compared using t-test, one-way analysis of variance (ANOVA) analysis and Spearman correlation analysis. Results ① There were differences between thoraco-dorsal pain group and patients without thoracodorsal pain group at the time of back muscle strength [(0.82±0.41) min vs (1.33±0.74) min, F=12.372, P=0.001]; ②Thoraco-dorsal pain in the AS group was mainly the middle and lower thoracic vertebrae, such as the inflammation of rib head and rib transverse process, facial arthritis, and spinous ligaments, etc. And the missed diagnosis rate of magnetic resonance imagin (MRI) was high. ③ In healthy control group, the anterior flexion strength of thoracodorsal pain group was signific-antly different from that of patients without thoracodorsal pain [(92.1 ±46.3) Nm vs (126.6±35.7) Nm, F=6.440, P=0.002]. ④ There was significant difference in spinal strength as well as left and right rotation strength between the thoracodorsal pain group and patients without thoracodorsal pain [(1.18 ±0.22) vs (1.05 ±0.17), F=10.044, P<0.01];⑤In the thoraco-dorsal pain group, the right/left index was related to BASDAI (r=-0.522, P=0.004). For spinal mobility, the right/left index was related to cross cutting faces to right ( r=0.435, P=0.021), cross cutting faces to left (r=0.528, P=0.004). In spinal strength, the right/left index was related to left turn (r=0.57, P=0.001); right lateral flexion (r=0.368, P=0.049) and left lateral flexion (r=0.369, P=0.049). Conclusion The thoracodorsal pain of AS is dominated by the middle and lower thoracic vertebrae, and the missed diagnosis rate of MRI is high. The imbalance of the left and right side of the spine is one of the factors of the thoracic back pain in AS.