Background Radiotherapy resistance is the main cause of low tumor regression for locally advanced rectum adenocarcinoma (READ). The biomarkers correlated to radiotherapy sensitivity and potential molecular mechanisms have not been completely elucidated. Methods A mRNA expression profile and a gene expression dataset of READ (GSE35452) were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) between radiotherapy responder and non-responder of READ were screened out. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for DEGs were performed. Random survival forest analysis was used to identified hub genes by randomForestSRC package. Based on CIBERSORT algorithm, Genomics of Drug Sensitivity in Cancer (GDSC) database, Gene set variation analysis (GSVA), enrichment analysis (GSEA), nomogram, motif enrichment and non-coding RNA network analyses, the associations between hub genes and immune cell infiltration, drug sensitivity, specific signaling pathways, prognosis prediction and TF – miRNA regulatory and ceRNA network were investigated. The expressions of hub genes in clinical samples were displayed with the online Human Protein Atlas (HPA). Results In total, 544 up-regulated and 575 down-regulated DEGs in READ were enrolled. Among that, three hubs including PLAGL2, ZNF337 and ALG10 were identified. These three hub genes were significantly associated with tumor immune infiltration, different immune-related genes and sensitivity of chemotherapeutic drugs. Also, they were correlated with the expression of various disease-related genes. In addition, GSVA and GSEA analysis revealed that different expression levels of PLAGL2, ZNF337 and ALG10 affected various signaling pathways related to disease progression. A nomogram and calibration curves based on three hub genes showed excellent prognosis predictive performance. And then, a regulatory network of transcription factor (ZBTB6) - mRNA (PLAGL2) and a ceRNA network of miRNA (has-miR-133b) - lncRNA were established. Finally, the results from HPA online database demonstrated the protein expression levels of PLAGL2, ZNF337 and ALG10 varied widely in READ patients. Conclusion These findings indicated that up-regulation of PLAGL2, ZNF337 and ALG10 in READ associated with radiotherapy response and involved in multiple process of cellular biology in tumor. They might be potential predictive biomarkers for radiotherapy sensitivity and prognosis for READ.
Background: Many neuroanatomical alterations have been detected in patients with tinnitus in previous studies. However, little is known about morphological and structural covariance network (SCN) changes before and after long-term sound therapy. This study aimed to explore alterations in brain anatomical and SCN changes in patients with idiopathic tinnitus using voxel-based morphometry (VBM) analysis 24 weeks before and after sound therapy. Methods: Thirty-three tinnitus patients underwent magnetic resonance imaging scans at baseline and after 24 weeks of sound therapy. Twenty-six age- and sex-matched healthy control (HC) individuals also underwent two scans over a 24-week interval; 3.0T MRI and high-resolution 3D structural images were acquired with a 3D-BRAVO pulse sequence. Structural image data preprocessing was performed using the VBM8 toolbox. The Tinnitus Handicap Inventory (THI) score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Two-way mixed model analysis of variance (ANOVA) and post hoc analyses were performed to determine differences between the two groups (patients and HCs) and between the two scans (at baseline and at the 24th week). Two-sample t tests, paired-samples t tests, and Pearson’s correlation analysis were used in the post hoc analysis.Results: Interaction effects between the two groups and the two scans demonstrated significantly different gray matter (GM) volume in the right parahippocampus gyrus, right caudate, left superior temporal gyrus, left cuneus gyrus and right calcarine gyrus; we found significantly decreased GM volume in the above five brain regions among the tinnitus patients before sound therapy (baseline) compared to that in the HC group. The 24-week sound therapy group demonstrated significantly greater brain volume compared with the baseline group among these brain regions. We did not find significant differences in brain regions between the 24-week sound therapy and HC groups. The SCN results showed that the left superior temporal gyrus and left rolandic operculum were significantly different in nodal efficiency, nodal degree centrality and nodal betweenness centrality after FDR correction. Decreased THI scores and GM volume changes between the left thalamus and right thalamus were not correlated. Conclusions: This study characterized the effect of sound therapy on brain GM volume, especially in the left superior temporal lobe. Notably, sound therapy had a normalizing effect on tinnitus patients.
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