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Artigo em Inglês | MEDLINE | ID: mdl-32065261


PURPOSE: To evaluate a radiomic approach for the stratification of diffuse gliomas with distinct prognosis and provide additional resolution of their clinicopathological and molecular characteristics. METHODS: For this retrospective study, a total of 704 radiomic features were extracted from the multi-channel MRI data of 166 diffuse gliomas. Survival-associated radiomic features were identified and submitted to distinguish glioma subtypes using consensus clustering. Multi-layered molecular data were used to observe the different clinical and molecular characteristics between radiomic subtypes. The relative profiles of an array of immune cell infiltrations were measured gene set variation analysis approach to explore differences in tumor immune microenvironment. RESULTS: A total of 6 categories, including 318 radiomic features were significantly correlated with the overall survival of glioma patients. Two subgroups with distinct prognosis were separated by consensus clustering of radiomic features that significantly associated with survival. Histological stage and molecular factors, including IDH status and MGMT promoter methylation status were significant differences between the two subtypes. Furthermore, gene functional enrichment analysis and immune infiltration pattern analysis also hinted that the inferior prognosis subtype may more response to immunotherapy. CONCLUSION: A radiomic model derived from multi-parameter MRI of the gliomas was successful in the risk stratification of diffuse glioma patients. These data suggested that radiomics provided an alternative approach for survival estimation and may improve clinical decision-making.

J Cell Physiol ; 235(4): 3823-3834, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31612488


Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package in R based on the RNA-sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype-Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time-dependent receiver operating characteristic curves and Kapan-Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941; p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.

Am J Transl Res ; 11(11): 6754-6774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814886


BACKGROUND: Thyroid carcinoma (TC) is a common malignancy of the endocrine system. This research aimed to examine the expression levels of miR-136-5p and metadherin (MTDH) in TC and unveil their potential targeting relationship. METHODS: TC microRNA (miRNA) microarray and miRNA-sequencing data were collected to evaluated miR-136-5p expression. We assessed the comprehensive expression of miR-136-5p by calculating the standard mean difference (SMD) and summary receiver operating characteristic curves (sROC). Subsequently, the miR-136-5p mimic and inhibitor were transfected into the TC B-CPAP cell, Thiazolyl Blue Tetrazolium Bromide (MTT) assay and cell apoptosis assay by FACS with Annexin V-/7-AAD double staining were performed to explore the biological role of miR-136-5p in the B-CPAP cell line. Prediction of target genes and potential biological function analysis of miR-136-5p were made using miRWalk2.0 and DAVID, respectively. Through target gene prediction, MTDH may be the candidate target gene of miR-136-5p. Subsequently, gene microarrays and RNA-sequencing data were also leveraged for MTDH expression. The meta-analysis method was conducted to evaluate the comprehensive expression level of MTDH. In addition, MTDH protein expression was identified using immunohistochemistry. The MTDH protein levels post-miR-136-5p transfection were verified by western blot, and the dual luciferase reporter assay was adapted to confirm the direct targeting relation between miR-136-5p and MTDH. RESULTS: The miR-136-5p level was remarkably downregulated in TC, the pooled SMD was -0.47 (95% CI: -0.70 to -0.23, I2=36.6%, P=0.192) and the area under the curve (AUC) of the sROC was 0.67 based on 543 cases of TC. MTT indicated that the overexpression of miR-136-5p dramatically inhibited the proliferation of B-CPAP cells. The cell apoptosis increased in the miR-136-5p mimic group compared to the negative control group. In addition, both MTDH mRNA and protein levels were markedly overexpressed, with the pooled SMD being 0.94 (95% CI: -0.35 to 2.24, I2=98.8%, P<0.001), and the AUC of the sROC being 0.85 with 1054 cases of TC. The MTDH protein level was significantly up-regulated in TC than in the non-carcinomic tissues by immunohistochemistry (8.292±1.717 vs. 2.618±2.570, P<0.001). Western blot indicated that MTDH protein expression was suppressed by miR-136-5p mimic in the B-CPAP cell line, which was further supported by the dual luciferase reporter assay. CONCLUSION: The miR-136-5p/MTDH axis may play a vital role in modulating TC tumorigenesis, providing new insight into possible molecular mechanisms of TC oncogenesis.