Dataset Information

Prognostic Value of a Three-DNA Methylation Biomarker in Patients with Soft Tissue Sarcoma.

ABSTRACT: Soft tissue sarcomas (STS) are a highly aggressive and heterogeneous group of malignant mesenchymal tumors. The prognosis of patients with advanced or metastatic STS remains poor, and the main therapy of STS patients combines primary surgery, radiotherapy, and chemotherapy. Aberrant DNA methylation shows close association with the pathogenesis and tumor progression. Therefore, DNA methylation biomarkers might have the potential in accurately predicting the survival of STS patients. In order to identify a prognostic biomarker based on DNA methylation sites, a comprehensive analysis of the DNA methylation profile of STS patients in the Cancer Genome Atlas (TCGA) database was performed. All samples were randomly divided into training and testing datasets. Cox proportional hazards regression analysis was performed to identify a prognostic biomarker that contains three DNA methylation sites. The Kaplan-Meier analysis demonstrated that the 3-DNA methylation biomarker discriminated patients into high-risk and low-risk groups, both in the training and in the testing datasets, and the area under the receiver operating characteristic curve values (AUCs) were 0.844 (P < 0.001, 95% CI: 0.740-0.948) and 0.710 (P = 0.002, 95% CI: 0.595-0.823), respectively. Besides, this biomarker presented superior prognostic performance in STS patients with different age, sex, tissue of origin, therapy, and histologic subtypes. Compared with other prognostic biomarkers, this biomarker tended to be a more precise prognostic factor in STS patients. Moreover, methylation sites in this biomarker might provide a new way for clinicians to make decisions regarding the intervention and assess the effectiveness of an individual therapeutic strategy.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7245661 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic Value of a Three-DNA Methylation Biomarker in Patients with Soft Tissue Sarcoma.

Chen Yuxiao Y Zhu Rui R Chen Min M Guo Wenna W Yang Xin X Xu Xin-Jian XJ Zhu Liucun L

Journal of oncology 20200515

Soft tissue sarcomas (STS) are a highly aggressive and heterogeneous group of malignant mesenchymal tumors. The prognosis of patients with advanced or metastatic STS remains poor, and the main therapy of STS patients combines primary surgery, radiotherapy, and chemotherapy. Aberrant DNA methylation shows close association with the pathogenesis and tumor progression. Therefore, DNA methylation biomarkers might have the potential in accurately predicting the survival of STS patients. In order to i ...[more]

PMID: 32508922

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Project description:The preoperative C-reactive protein/Albumin ratio (CAR) is valuable for predicting the prognosis of patients with various types of cancers. The aim of the present study is to investigate the prognostic value of the preoperative CAR and compare it with other systemic inflammatory response markers in patients with soft tissue sarcoma (STS).This retrospective study included 206 patients with STS. The optimal cutoff value of the CAR was determined by receiver operating characteristic (ROC) analysis. The impact of the CAR and other clinicopathological features on overall survival (OS) and disease-free survival (DFS) was evaluated using univariate and multivariate Cox regression analyses. Kaplan-Meier survival analyses were used to compare groups classified by the CAR. Additionally, the area under the receiver operating characteristic curve (AUC) was used to compare the predictive ability of the CAR, high-sensitivity modified Glasgow prognostic score (Hs-mGPS), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR).The optimal cut-off value of the CAR was 0.1035 according to the ROC analysis. An increased CAR (?0.1035) was significantly associated with older age, larger tumor size, deep tumor location, higher tumor grade and more advanced American Joint Committee on Cancer (AJCC) stage (all P<0.05). Patients with an elevated CAR (?0.1035) exhibited a shorter median survival time and lower 5-year OS rate than those with a CAR<0.1035 (68.2 vs 115.8 months, P = 0.000; 44.6% vs 80.9%, P = 0.000, respectively). The results of a multivariate analysis indicated that the CAR (Hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.47-4.14, P = 0.001) was an independent prognostic factor for OS along with tumor grade (P<0.05). Additionally, the CAR exhibited a greater AUC value (0.662) than the NLR and PLR, but the value was equal to the Hs-mGPS.The preoperative CAR is an independent prognostic factor predicting prognosis in STS and exhibits superior prognostic ability compared to the established inflammation-based prognostic indices.

Project description:High-grade soft-tissue sarcoma (STS) is a highly malignant neoplasm with a poor overall prognosis. Numerous prognostic factors determine tumor progression and patient outcomes. Various immune-associated cells identified in the tumor microenvironment have important roles in various tumor types. The present study was performed to evaluate the expression of immune-associated genes and to elucidate the association between these genes and the prognosis in high-grade STS. A total of 12 formalin-fixed, paraffin-embedded tissue samples of high-grade STS were subjected to gene expression analysis using the NanoString nCounter® System and another 35 samples were used for immunohistochemistry. For comparative analysis, the patients were divided into two groups according to overall survival (OS). The expression levels of 770 genes were first analyzed using the nCounter® PanCancer Immune Profiling Panel. Immunohistochemistry was then performed for the most significantly altered genes. Subsequently, the association between gene expression and prognosis of high-grade STS was evaluated. Of the 770 immune-associated genes analyzed, several genes were identified as being differentially expressed between the two groups. Based on gene expression levels and fold change, 13 representative genes were identified; 7 of the 13 candidate genes (C3, CD36, DOCK9, FCER2, FOS, HLA-DRB4 and NCAM1) were significantly overexpressed in the poor prognosis group, while the other 6 immune-associated genes (BIRC5, DUSP4, FOXP3, HLA-DQA1, HLA-DQB1 and LAG3) were increased in the good prognosis group. By immunohistochemistry, the expression of the 13 immune-associated genes was confirmed to be significantly different between the two groups. Expression of HLA-DQA1, HLA-DQB1 and HLA-DRB4 was observed in 74.3, 34.3 and 48.6% of tumors, respectively. HLA-DQA1 and HLA-DQB1 were significantly decreased, whereas HLA-DRB4 was significantly increased in the poor prognosis group. Of note, expression of HLA-DQA1 was associated with a significantly longer OS (P=0.028). In conclusion, HLA-DQA1 expression was significantly associated with long-term survival and may therefore be an immune biomarker for good prognosis in high-grade STS.

Dataset Information

Prognostic Value of a Three-DNA Methylation Biomarker in Patients with Soft Tissue Sarcoma.

Publications

Prognostic Value of a Three-DNA Methylation Biomarker in Patients with Soft Tissue Sarcoma.

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