Dataset Information

A Prognostic Molecular Signature of N?-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database.

ABSTRACT: BACKGROUND Soft-tissue sarcomas are a group of heterogeneous and rare mesenchymal tumors with aggressive behavior. We aimed to identify the molecular signatures of N?-methyladenosine (m6A) methylation regulators associated with patient prognosis using The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS To evaluate the role of m?A in soft-tissue sarcomas, genomic and clinical data were downloaded from TCGA. The copy number variations (CNVs) and mutations of m6A regulators were analyzed. RESULTS Alterations of m?A regulators were common, and ALKBH5 showed the highest frequency of copy number gain, while ZC3H13 had the highest frequency of loss. CNVs and mutations were closely correlated with histology (P<0.001) and tumor size (P=0.040), and CNVs were correlated with mRNA expression. Furthermore, patients with gains of METTL16, RMB15, RMB15B, YTHDC, and YTHDF3 displayed poorer overall survival (OS), and patients with gains of RBM15 and YTHDC2 and loss of IGF2BP1 had poorer disease-free survival (DFS). Further analysis indicated that CNVs and mutations of KIAA1429, YTHDF3, and IGF2BP1 were independent risk factors predicting OS and DFS. Gain of "writers" with loss of "erasers" led to worse OS than gain of "writers". Genes involved in JAK2 oncogenic signature were enriched in cases of higher expressions of METTL16, YTHDC2, and YTHDF3. Similarly, the core serum response signature was enriched in patients with higher expressions of IGF2BP1, METTL16, RBM15, and YTHDC2. CONCLUSIONS Our study provides a useful molecular tool to predict the outcome of soft-tissue sarcomas and deepens our understanding of the molecular mechanisms of the development of the disease.

SUBMITTER: Hou M

PROVIDER: S-EPMC7780893 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database.

Hou Mingming M Guo Xiaohui X Chen Yu Y Cong Lidan L Pan Changwu C

Medical science monitor : international medical journal of experimental and clinical research 20201228

BACKGROUND Soft-tissue sarcomas are a group of heterogeneous and rare mesenchymal tumors with aggressive behavior. We aimed to identify the molecular signatures of N⁶-methyladenosine (m6A) methylation regulators associated with patient prognosis using The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS To evaluate the role of m⁶A in soft-tissue sarcomas, genomic and clinical data were downloaded from TCGA. The copy number variations (CNVs) and mutations of m6A regulators were analyzed. ...[more]

PMID: 33370249

Similar Datasets

Project description:BackgroundSoft-tissue sarcomas (STS) constitute a rare group of heterogeneous mesenchymal tumours containing more than 100 histologic subtypes. Here, we investigate whether, and if so, to what extent, skeletal metastases affect the outcome of patients with advanced or metastatic disease.Materials and methodsSelected patients participated in five clinical trials of EORTC-STBSG. Individuals were included if they started treatment with an active drug and had advanced/metastatic STS. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). Univariate and multivariate pooled analyses (after correcting for 12 covariates) were employed with Kaplan-Meier and Cox regression to model the impact of bone metastasis at presentation per treatment line stratified by study. For the subset of patients with bone metastasis, the impact of another metastatic organ site was explored with multivariate Cox regression models.Results565 out of 1034 (54.6%) patients received first-line systemic treatment for locally advanced or metastatic disease. Bone metastases were present in 140 patients (77 first-line, 63 second-line or higher). The unadjusted difference in OS/PFS with or without bone metastasis was statistically significant only for first-line patients. For OS, the adjusted hazard ratios for bone metastasis presence were 1.33 (95%-CI: 0.99-1.78) and 1.11 (95%-CI: 0.81-1.52) for first-line/second-line or higher treated patients, respectively. Likewise, the adjusted hazard ratios for PFS were 1.31 (95%-CI: 1.00-1.73) and 1.07 (95%-CI: 0.80-1.43). Effects were not statistically significant, despite a trend in first-line patients for both endpoints. Subgroup analyses indicated bone and lymph node metastasis as the most detrimental combination for OS and bone and lung metastasis for PFS.ConclusionsAdult STS patients receiving palliative systemic therapy with bone metastasis carried an overall worse prognosis than STS patients without bone metastases. Skeletal metastasis was detrimental for both OS and PFS, independent of the treatment line. Findings may have implications for the management of these patients.

Dataset Information

A Prognostic Molecular Signature of N?-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database.

Publications

A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets