scholarly journals OS09.1 Radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with lower grade glioma in the Cancer Genome Atlas (TCGA) Dataset

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii18-iii18
Author(s):  
B. Jang ◽  
I. Kim
2020 ◽  
Vol 78 (1) ◽  
pp. 34-38
Author(s):  
Burcu BITERGE-SUT

Abstract Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. Objective: The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). Methods: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. Results: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. Conclusions: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhizheng Liu ◽  
Hongliang Meng ◽  
Miaoxian Fang ◽  
Wenlong Guo

Background. Lower-grade glioma is an intracranial cancer that may develop into glioblastoma with high mortality. The main objective of our study is to develop microRNA for LGG patients which will provide novel prognostic biomarkers along with therapeutic targets. Methods. Clinicopathological data of LGG patients and their RNA expression profile were downloaded through The Cancer Genome Atlas Relevant expression profiles of RNA, and clinicopathological data of the LGG patients had been extracted from the database of “The Cancer Genome Atlas.” Differential expression analysis had been conducted for identification of the differentially expressed microRNAs as well as mRNAs in LGG samples and normal ones. ROC curves and K–M plots were plotted to confirm performance and for predictive accuracy. For the confirmation of microRNAs as an independent prognostic factor, an independent prognosis analysis was conducted. Moreover, target differentially expressed genes of these identified prognostic microRNAs that were extracted and protein-protein interaction networks were developed. Moreover, the biological functions of signature were determined through Genome Ontology analysis, genome pathway analysis, and Kyoto Encyclopedia of Genes. Results. 7-microRNA signature was identified that has the ability of categorization of individuals with LGG into high- and low-risk groups on the basis of significant difference in survival during training and testing cohorts (P < 0.001). The 7-microRNA signature had appeared to be robust in predictive accuracy (all AUC> 0.65). It was also approved with multivariate Cox regression along with some traditional clinical practices that we can use 7-microRNA signature for therapeutic purposes as a self-regulating predictive OS factor (P < 0.001). KEGG and Gene Ontology (GO) analyses reported that 7-microRNAs had mainly developed in important pathways related with glioma, e.g., the “cAMP signaling pathway,” “glutamatergic synapses,” and “calcium signaling pathway”. Conclusion. A newly discovered 7-microRNA signature could be a potential target for the diagnosis and treatment for LGG patients.


2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 54-54
Author(s):  
In Ah Kim ◽  
Bum Sup Jang

54 Background: A radiosensitivity gene signature that included 31 genes was identified using microarray data from NCI-60 cancer cells; however, this has not been validated in independent datasets for breast cancer patients. We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. Methods: We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset using bioinformatic tools. To validate the gene signature, 1,065 patients (or samples) were selected and divided into two clusters using a consensus clustering algorithm based on their radiosensitive (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1. The relationship between the RS/RR groups and PD-L1 status was also assessed. The prognostic value was evaluated by Kaplan-Meier analysis and Cox proportional hazard models. Results: Patents assigned to the RS group had better 5-year recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (89% vs. 75%, p = 0.017) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p<0.001) than the RR group. In the PD-L1-high group, the RS group had better 5-year RFS rate compared to the RR group (89% vs. 72%, p = 0.015), and this difference was also significant by Cox-hazard proportional analysis. Conclusions: The radiosensitivity gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1 therapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.


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