Purpose
Growing evidence has demonstrated an indispensable role for N6‐methyladenosine (m6A) in human diseases, but the copy number variations (CNVs) of m6A regulatory genes in bladder cancer (BLCA) ...remains largely unknown.
Methods
We investigated the CNVs on all known m6A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database.
Results
CNV events of m6A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer‐related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6A regulatory genes were correlated with specific kinds of immune infiltrates.
Conclusions
There are significant correlations between m6A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.
We investigated the CNV events on all known m6A regulatory genes which were obtained from the Cancer Genome Atlas (TCGA) database through bioinformatics analysis of prognosis as well as immune infiltrates of BLCA patients. We found that CNVs of METTL3 associated with the overall survival (OS). Furthermore, RNA methyltransferases may affect the outcome of tumor immunotherapy via regulating immune infiltrates.
RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, ...little is known regarding their possible roles in STS.
RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines.
CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib.
CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.
•CNV of RNA regulatory genes was frequently observed in STS.•CNV of METTL4 was associated with OS in STS, including LMS and DDLPS.•In STS and DDLPS, the diploid CN of METTL4 possessed lower methylation level of cg12105018, representing better OS.•GCT was the most sensitive STS cell line to Temozolomide and Olaparib according to drug sensitivity analysis and MTT assays.•CNV of METTL4 could be a prognostic and therapy-response biomarker for STS.
Background
Brachial plexus injury is recognized as one of the most severe clinical challenges due to the complex anatomical configuration of the brachial plexus and its propensity for variation, ...which complicates safe clinical interventions. This study aimed to ascertain the prevalence and characterize the types of brachial plexus variations, and to elucidate their clinical implications.
Materials and Methods
We conducted meticulous dissections of 60 formalin‐fixed cadavers' upper arm, axilla and lower neck to reveal and assess the roots, trunks, divisions, cords, and branches of the brachial plexus. The pattern of branching was noted by groups of dissecting medical students and confirmed by the senior anatomists. The variations discovered were record and photographed using a digital camera for further analysis.
Results
Variations in the brachial plexus were identified in 40 of the 60 cadavers, yielding a prevalence rate of 66.7%. These variations were classified into root anomalies (2.1%), trunk anomalies (8.5%), division anomalies (2.1%), and cord anomalies (4.3%). Notably, anomalies in communicating branches were observed in 39 cadavers (83.0%): 14 with bilateral anomalies, 14 with anomalies on the left side, and 11 on the right side. These communicating branches formed connections between the roots and other segments, including trunks, cords, and terminal nerves, and involved the median, musculocutaneous, and ulnar nerves.
Conclusion
The frequency and diversity of brachial plexus variations, particularly in communicating branches, are significant in cadavers. It is imperative that these variations are carefully considered during the diagnostic process, treatment planning, and prior to procedures such as supraclavicular brachial plexus blocks and nerve transfers, to mitigate the risk of iatrogenic complications.
Growing evidence has demonstrated an indispensable role for N
-methyladenosine (m
A) in human diseases, but the copy number variations (CNVs) of m
A regulatory genes in bladder cancer (BLCA) remains ...largely unknown.
We investigated the CNVs on all known m
A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m
A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database.
CNV events of m
A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer-related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m
A regulatory genes were correlated with specific kinds of immune infiltrates.
There are significant correlations between m
A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.
PURPOSEGrowing evidence has demonstrated an indispensable role for N6 -methyladenosine (m6 A) in human diseases, but the copy number variations (CNVs) of m6 A regulatory genes in bladder cancer ...(BLCA) remains largely unknown. METHODSWe investigated the CNVs on all known m6 A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6 A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. RESULTSCNV events of m6 A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer-related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6 A regulatory genes were correlated with specific kinds of immune infiltrates. CONCLUSIONSThere are significant correlations between m6 A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.
The aim of this study is to determine the incidence and explore the types of aortic arch branch variations found in our cadavers.
The types and incidence of aortic branch variations in 120 cadavers ...were analysed after careful dissection.
One hundred and six of 120 cadavers had normal aortic arch branches and gave rise to usual branches, namely the brachiocephalic trunk, the left common carotid artery and the left subclavian artery. The remaining 14 cadavers had 2 basic types of branch variations, thus accounting for an incidence of 11.67%. A total of 9 aortic arches emitted 4 branches; the brachiocephalic trunk, the left common carotid artery, the left vertebral artery and the left subclavian artery (incidence 7.5%). The second subgroup of 5 cadavers also emitted 4 aortic branches: the right common carotid artery, the left common carotid artery, the left subclavian artery and the right subclavian artery (incidence 4.16%). In this group, the right subclavian artery sprung as a distal branch of the aortic arch (descending), thus making a vascular ring that takes a superoposterior course round the back of the trachea and the oesophagus to reach the right side. There was a single cadaver, different from the other 4 aortic branches of the second group which had a common origin for the common carotid arteries, while the left subclavian artery and distally placed right subclavian artery were present. We did not observe any Kommerell's aortic diverticula.
The variations of aortic arch branching are complex and diverse due to varied possible alterations in the embryological processes. There is an imperative need for further research on these variations to elucidate the possible relationships with clinical diagnostic or surgical events.
To explore the potential functions and mechanism of
.methyladenosine (m
A) abnormality of RNAs in nucleus pulposus from the intervertebral disc degeneration (IDD).
We performed rat model, m
A ...epitranscriptomic microarray, bioinformatics analysis and metabolomics.
In IDD, most of the differentially methylated RNAs showed a significant demethylation situation. The competing endogenous RNA network
/
/
combining downstream Wnt pathway were identified in bioinformatics analysis. For metabolomics, activation of Wnt pathway led to reprogramming of glucose metabolism and enzyme activation of
. Finally, quantitative real-time PCR and methylated RNA immunoprecipitation coupled with quantitative real-time PCR revealed the positive correlation between demethylation of
and expression of both
and
.
might be demethylated by ZFP217, activating FTO and
/
/
/Wnt played a crucial role in IDD.
PDF
