Identification and validation of a gene expression signature that predicts outcome in malignant glioma patients

Kawaguchi, Atsushı; Yajima, Naoki; Komohara, Yoshihiro; Aoki, Hiroshi; Tsuchiya, Naoto; Homma, Jumpei; Sano, Masakazu; Natsumeda, Manabu; Uzuka, Takeo; Saitoh, Akihiko; Takahashi, Hideaki; Sakai, Yuko; Takahashi, Hitoshi; Fujii, Yukihiko; Kakuma, Tatsuyuki; Yamanaka, Ryuya

doi:10.3892/ijo.2011.1240

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…Following RNA isolation and cDNA synthesis, biotin-labeled cRNA was prepared by Enzo® BioArray TM HighYield TM RNA transcript label kit (Enzo life sciences, INC), then hybridized to the Affymetrix Gene Chip Human Genome U133 Plus 2.0 Array (Santa Clara, CA). Differentially expressed lncRNAs were analyzed as described previously [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

et al. 2017

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BackgroundSeveral of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood.MethodsLncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation. The role of HOXD-AS1 in HCC cells was assessed both in vitro and in vivo. ceRNA function of HOXD-AS1 was evaluated by RNA immunoprecipitation and biotin-coupled miRNA pull down assays.ResultsIn this study, we found that HOXD-AS1 was significantly upregulated in HCC tissues. Clinical investigation demonstrated high expression level of HOXD-AS1 was associated with poor prognosis and high tumor node metastasis stage of HCC patients, and was an independent risk factor for survival. Moreover, our results revealed that STAT3 could specifically interact with the promoter of HOXD-AS1 and activate HOXD-AS1 transcription. Knockdown of HOXD-AS1 significantly inhibited migration and invasion of HCC cells in vitro and distant lung metastasis in vivo. Additionally, HOXD-AS1 was enriched in the cytoplasm, and shared miRNA response elements with SOX4. Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA-mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis.ConclusionsIn summary, HOXD-AS1 is a prognostic marker for HCC patients and it may play a pro-metastatic role in hepatocarcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0680-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

et al. 2017

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Identification of potential biomarkers related to glioma survival by gene expression profile analysis

et al. 2019

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Background Recent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. However, most of these genes can only be used appropriately for patients with specific grades of gliomas. Methods In this study, we aimed to identify survival-relevant genes shared between glioblastoma multiforme (GBM) and lower-grade glioma (LGG), which could be used as potential biomarkers to classify patients into different risk groups. Cox proportional hazard regression model (Cox model) was used to extract relative genes, and effectiveness of genes was estimated against random forest regression. Finally, risk models were constructed with logistic regression. Results We identified 104 key genes that were shared between GBM and LGG, which could be significantly correlated with patients’ survival based on next-generation sequencing data obtained from The Cancer Genome Atlas for gene expression analysis. The effectiveness of these genes in the survival prediction of GBM and LGG was evaluated, and the average receiver operating characteristic curve (ROC) area under the curve values ranged from 0.7 to 0.8. Gene set enrichment analysis revealed that these genes were involved in eight significant pathways and 23 molecular functions. Moreover, the expressions of ten ( CTSZ, EFEMP2 , ITGA5 , KDELR2 , MDK , MICALL2, MAP 2 K3 , PLAUR , SERPINE1 , and SOCS3 ) of these genes were significantly higher in GBM than in LGG, and comparing their expression levels to those of the proposed control genes ( TBP , IPO8 , and SDHA ) could have the potential capability to classify patients into high- and low- risk groups, which differ significantly in the overall survival. Signatures of candidate genes were validated, by multiple microarray datasets from Gene Expression Omnibus, to increase the robustness of using these potential prognostic factors. In both the GBM and LGG cohort study, most of the patients in the high-risk group had the IDH1 wild-type gene, and those in the low-risk group had IDH1 mutations. Moreover, most of the high-risk patients with LGG possessed a 1p/19q-noncodeletion. Conclusion In this study, we identified survival relevant genes which were shared between GBM and LGG, and those enabled to classify patients into high- and low-risk groups based on expression level analysis. Both the risk groups could be correlated with the well-known genetic variants, thus suggesting their potential prognostic value in clinical application. Electronic supplementary material The online version of this article (10.1186/s1...

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Pathway and Network Analysis in Glioma with the Partial Least Squares Method

Gu²,

Shou³

2014

Asian Pacific Journal of Cancer Prevention

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Identification and validation of a gene expression signature that predicts outcome in malignant glioma patients

Cited by 3 publications

References 31 publications

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

Identification of potential biomarkers related to glioma survival by gene expression profile analysis

Pathway and Network Analysis in Glioma with the Partial Least Squares Method

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