Autophagy-related gene expression is an independent prognostic indicator of glioma.
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC5617400 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Autophagy-related gene expression is an independent prognostic indicator of glioma.
Zhang Huixue H Lu Xiaoyan X Wang Ning N Wang Jianjian J Cao Yuze Y Wang Tianfeng T Zhou Xueling X Jiao Yang Y Yang Lei L Wang Xiaokun X Cong Lin L Li Jianlong J Li Jie J Ma He-Ping HP Pan Yonghui Y Ning Shangwei S Wang Lihua L
Oncotarget 20170509 37
In this study, we identified 74 differentially expressed autophagy-related genes in glioma patients. Analysis using a Cox proportional hazard regression model showed that MAPK8IP1 and SH3GLB1, two autophagy-related genes, were associated with the prognostic signature for glioma. Glioma patients from the CGGA batches 1 and 2, GSE4412 and TCGA datasets could be divided into high- and low-risk groups with different survival times based on levels of MAPK8IP1 and SH3GLB1 expression. The autophagy-rel ...[more]
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Project description:PurposeAutophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment; however, autophagy-related gene sets have rarely been analyzed in glioblastoma. The purpose of this study was to evaluate the prognostic significance of autophagy-related genes in patients with glioblastoma.Patients and methodsHere, we collected whole transcriptome expression data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets to explore the relationship between autophagy-related gene expression and glioblastoma prognosis. R language was the primary analysis and drawing tool.ResultsWe screened 531 autophagy-related genes and identified 14 associated with overall survival in data from 986 patients with glioblastoma. Patients could be clustered into two groups (high and low risk) using expression data from the 14 associated genes, based on significant differences in clinicopathology and prognosis. Next, we constructed a signature based on the 14 genes and found that most patients designated high risk using our gene signature were IDH wild-type, MGMT promoter non-methylated, and likely to have more malignant tumor subtypes (including classical and mesenchymal subtypes). Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with their low-risk counterparts. Cox regression analysis further confirmed the independent prognostic value of our 14 gene signature. Moreover, functional and ESTIMATE analyses revealed enrichment of immune and inflammatory responses in the high-risk group.ConclusionIn this study, we identified a novel autophagy-related signature for the prediction of prognosis in patients with glioblastoma.
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Project description:Background: Analysis of the differentially expressed genes between lower grade glioma (LGG) and glioblastoma (GBM) will identify genes involved in a more aggressive phenotype of glioma. Methods: Differentially expressed genes between GBM and LGG were identified using published datasets. Kaplan-Meier estimator was used to determine the overall survival of different groups of glioma patients. The biological functions of CDHR1 in glioma were tested using CCK-8 and trans-well assays. Results: CCDC109B, CD58, CLIC1, EFEMP2, EMP3, LAMC1, LGALS1, PDLIM1 and TNFRSF1A were over-expressed, while, CDHR1 was down-regulated in GBM in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE4412 and GSE43378 datasets. Compared with normal brain tissues, CDHR1 was down-regulated in glioma tissues. And low expression of CDHR1 was an unfavorable prognostic factor in glioma. Moreover, CDHR1 was lowly expressed in mesenchymal GBM subtype and lower expression of CDHR1 was associated with the worse clinical prognosis of GBM. Furthermore, CDHR1 was down-regulated in astrocytoma LGG subtype and low expression of CDHR1 was a bad prognosis of LGG. CDHR1 expression levels were also associated with IDH mutation. IDH mutant LGG or GBM patients were with higher CDHR1 expression. High expression of CDHR1 was a favorable prognosis in IDH mutant or IDH wild type LGG patients. CHDR1 expression was associated with MGMT methylation and CDHR1 was down-regulated in chemotherapy un-responsive LGG patients. CDHR1 was an independent prognostic factor and negatively associated with EMP3 expression. Glioma patients with low CDHR1 and high EMP3 expression had worse clinical outcomes. At last, we showed that over-expression of CDHR1 could inhibit glioma cell growth and invasion. Conclusion: Low expression of CDHR1 was an independent unfavorable prognostic factor in glioma.
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Project description:BackgroundSeizure-related 6 homolog (mouse)-like 2 (SEZ6L2) is a type 1 transmembrane protein that is primarily expressed in the brain . In recent reports, SEZ6L2 has been found to be overexpressed in some cancers and can drive the progression of tumors. However, its function and mechanism in thyroid cancer remain unclear.MethodsIn this article ,we searched for the SEZ6L2 expressions in Pan-cancer on TCGA (The Cancer Genome Atlas) and evaluated these data using the TIMER2 method. Then, the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was collected in human protein mapping (HPA) data. And we used CIBERSORT to assess the association between the levels of SEZ6L2 expression and the number of various immune cells in papillary thyroid carcinoma (PTC) tissue. Finally, Gene Expression Omnibus (GEO) analyses, real-time quantitative polymerase chain reaction (qRT-PCR) of tissues, and immunohistochemical staining were used to detect the result.ResultsThe article illustrated that a large number of cancers had a higher expression of SEZ6L2 compared to the control tissues. And the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was considerably elevated compared to that in normal tissues SEZ6L2 was elevated in thyroid carcinoma (THCA) tissue, besides, GEO analyses, qRT-PCR of tissues, and immunohistochemical staining were conducted to test the results. Finally, the Kaplan-Meier survival analysis illustrated that the increased expression of SEZ6L2 was correlated with a dismal prognosis-higher SEZ6L2 is associated with shorter survival. And the univariate analysis illustrated that T stage, SEZ6L2 and Pathologic stage were related to the overall survival (OS), multivariate analysis stated that elevated expression of SEZ6L2 was an independent risk factor that affected progression-free interval (PFI) (P<0.05). Consequently, we found that the expression of SEZ6L2 was correlated with tumor-infiltrating immune cells by TIMER.ConclusionsSEZ6L2 was upregulated in patients with THCA and that increased expression of SEZ6L2 was related with clinical progression and was regarded as an independent risk factor for PFI. In THCA patients, the expression of SEZ6L2 could be a significant prognostic factor, which is expected to be a prospective biomarker for THCA in the future.
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