Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma

Abstract

Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES. mRNA expression profile chip data sets GSE17674, GSE17679 and GSE45544 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the R software limma package, and functional and pathway enrichment analyses were performed using the enrichplot package and GSEA software. The NetworkAnalyst online tool, as well as Cytoscape and its plug-ins cytoHubba and NetworkAnalyzer, were used to construct a protein-protein interaction network (PPI) and conduct module analysis to screen key (hub) genes. LABSO COX regression and overall survival (OS) analysis of the Hub genes were performed. A total of 211 DEGs were obtained by integrating and analyzing the three data sets. The functions and pathways of the DEGs were mainly associated with the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes, as well as the Rac1, cell cycle and P53 signaling pathways. A total of one important module and 20 hub genes were screened from the PPI network using the Maximum Correlation Criteria algorithm of cytoHubba. LASSO COX regression results revealed that titin (TTN), fast skeletal muscle troponin T, skeletal muscle actin α-actin, nebulin, troponin C type 2 (fast), myosin light-chain 3 (MYL3), slow skeletal muscle troponin T (TNNT1), myosin-binding protein C1 slow-type, tropomyosin 3 and myosin heavy-chain 7 were associated with prognosis in patients with ES. The Kaplan-Meier curves demonstrated that high mRNA expression levels of TNNT1 (P<0.001), TTN (P=0.049), titin-cap (P=0.04), tropomodulin 1 (P=0.011), troponin I2 fast skeletal type (P=0.021) and MYL3 (P=0.017) were associated with poor OS in patients with ES. In conclusion, the DEGs identified in the present study may be key genes in the pathogenesis of ES, three of which, namely TNNT1, TTN and MYL3, may be potential prognostic biomarkers for ES.

Transcriptomic and immunophenotypic characterization of two cases of adamantinoma‐like Ewing sarcoma of the thyroid gland

“…Further query at the Molecular Signature Database 10,11 showed that 53 (15.5%) of those 341 genes overlapped with a gene set overexpressed in mesenchymal stem cells with induced expression of the EWSR1::FLI1 fusion transcript 15 (Figure 4A). Of those, NKX2‐2 has been extensively studied in BST ES 16 and TNNT1 seems to be a promising biomarker of adverse behaviour 17 …”

“…Of those, NKX2-2 has been extensively studied in BST ES 16 and TNNT1 seems to be a promising biomarker of adverse behaviour. 17 In ALES 461 genes where differentially expressed from BST ES, of which 395 (85.7%) overexpressed and 66 (14.3%) underexpressed. In relation to nonneoplastic thyroid tissue ALES had differential expression of 1346 genes, of which 682 (50.7%) were upregulated and 664 (49.3%) were underexpressed.…”

Transcriptomic Profile of Canine Mammary Ductal Carcinoma

“…On the other hand, high expression of TTN and MYL3 genes can be described as a biomarker of a worse prognosis in Ewing’s sarcoma [ 52 ]. TTN was also reported to be more expressed in gastric adenocarcinoma [ 53 ].…”

Construction of a Prognostic Signature in Ewing’s Sarcoma: Based On Metabolism-Related Genes

“…According to GO and KEGG analysis, we discovered that these MRGs in uenced the prognosis of Ewing's sarcoma mainly through the following functions and pathways, including small molecule catabolic process, coenzyme binding, arginine and proline metabolism, tyrosine metabolism and fatty acid degradation. The role of the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes in Ewing's sarcoma development and prognosis has been identi ed and validated by studies [16] . In the mitochondria of malignantly proliferating tumor cells, some necessary metabolic processes occur, such as the oxidative metabolism of glucose and glutamine to produce citrate and acetyl-CoA, which are involved in the synthesis of lipids.…”