Prognostic Value of a Nine‐Gene Signature in Glioma Patients Based on <scp>mRNA</scp> Expression Profiling

Bao, Zhaoshi; Li, Mingyang; Wang, Jiayin; Zhang, Chuanbao; Wang, Hongjun; Yan, Wei; Liu, Yanwei; Zhang, Wei; Chen, Ling; Jiang, Tao

doi:10.1111/cns.12171

Cited by 85 publications

(61 citation statements)

References 36 publications

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“…Elevated levels of Rab1A DNA, mRNA or protein have been reported previously in human CRC [8], gliomas [14], HCC [18], prostate cancer [15] and tongue squamous carcinomas [16]. Our study for the first time shows that Rab1A is significantly overexpressed in lung cancer.…”

Section: Discussionsupporting

confidence: 78%

“…Recently, a growing body of evidence has suggested that the Rab1A protein has additional functions beyond its role in vesicular transport, including nutrient sensing [8] and signaling [9], cell migration [10] and regulation of autophagy [11]. Moreover, aberrant expression of Rab1A has been linked to a range of human diseases including cardiomyopathy [12], Parkinson's disease [13] and cancer [8, 14-19]. …”

Section: Introductionmentioning

confidence: 99%

“…Rab1A has been identified as a colorectal oncogene, and elevated expression of Rab1A has been reported in multiple cancer types, including colorectal cancer (CRC) [8], hepatocellular carcinoma (HCC) [18], glioma [14], prostate cancer [15, 17], tongue squamous carcinoma [16] and cervical cancer [19]. Overexpression of Rab1A is correlated with a poor prognosis and has been proposed to promote tumor progression by activating the mTORC1 signaling pathway in CRC and HCC, indicating that Rab1A might be a valuable therapeutic target for personalized therapy [8].…”

Section: Introductionmentioning

confidence: 99%

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Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage

Wang

Liu

Qin

et al. 2016

Aging

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Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined. The results demonstrated that Rab1A was significantly overexpressed in the different histological types of lung cancer as compared to non-cancerous tissues, and Rab1A expression was correlated with tumor volume and stage. In a large panel of lung cancer cell lines, high Rab1A expression was observed as compared to a normal lung/bronchus epithelial cell line. However, Rab1A protein levels were not correlated with mTORC1 (P-S6K1), mTORC2 (P-AKT), MEK (P-ERK), JNK (P-c-Jun) or p38MAPK (P-MK2) signaling. Rab1A knockdown had no effect on mTOR signaling or cell growth. These data suggested that Rab1A may be involved in the pathogenesis of human lung cancer in an mTOR- and MAPK-independent manner.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage

Wang

Liu

Qin

et al. 2016

Aging

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“…IDH mutations are an early, possibly driver, event for LGG (Watanabe et al, 2009), and clinical trials of IDH inhibitors are underway (Dimitrov et al, 2015). Many studies have demonstrated that survival outcome of LGG patients is significantly different based on the status of IDH gene mutation, 1p/19q codeletion, telomerase reverse transcriptase ( TERT ) promoter mutation, ATRX gene mutation, CpG island methylator phenotypes (CIMP), O-6-methylguanine-DNA methytransferase ( MGMT) promoter methylation, the neural stem cell gene nestin ( NES ) expression and mRNA expression signatures by multiple genes (Cancer Genome Atlas Research et al, 2015, Eckel-Passow et al, 2015, Ceccarelli et al, 2016, Chan et al, 2015, Noushmehr et al, 2010, Turcan et al, 2012, Hatanpaa et al, 2014, Siegal, 2015, Bao et al, 2014, Zhang et al, 2015). The classification by CIMP status after filtering IDH mutation status revealed biologically discrete subsets having different clinic survival outcomes in diffuse gliomas (Ceccarelli et al, 2016), supporting the principle that IDH mutation status plus other molecular biomarkers can enhance the prognostic value for certain molecularly distinct subsets of LGG patients.…”

Section: Introductionmentioning

confidence: 99%

SHOX2 is a Potent Independent Biomarker to Predict Survival of WHO Grade II–III Diffuse Gliomas

et al. 2016

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BackgroundDiffuse gliomas, grades II and III, hereafter called lower-grade gliomas (LGG), have variable, difficult to predict clinical courses, resulting in multiple studies to identify prognostic biomarkers. The purpose of this study was to assess expression or methylation of the homeobox family gene SHOX2 as independent markers for LGG survival.MethodsWe downloaded publically available glioma datasets for gene expression and methylation. The Cancer Genome Atlas (TCGA) (LGG, n = 516) was used as a training set, and three other expression datasets (n = 308) and three other methylation datasets (n = 320), were used for validation. We performed Kaplan-Meier survival curves and univariate and multivariate Cox regression model analyses.FindingsSHOX2 expression and gene body methylation varied among LGG patients and highly significantly predicted poor overall survival. While they were tightly correlated, SHOX2 expression appeared more potent as a prognostic marker and was used for most further studies. The SHOX2 prognostic roles were maintained after analyses by histology subtypes or tumor grade. We found that the combination of SHOX2 expression and IDH genotype status identified a subset of LGG patients with IDH wild-type (IDHwt) and low SHOX2 expression with considerably favorable survival. We further investigated the combination of SHOX2 with other known clinically relevant markers of LGG (TERT expression, 1p/19q chromosome co-deletion, MGMT methylation, ATRX mutation and NES expression). When combined with SHOX2 expression, we identified subsets of LGG patients with significantly favorable survival outcomes, especially in the subgroup with worse prognosis for each individual marker. Finally, multivariate analysis demonstrated that SHOX2 was a potent independent survival marker.InterpretationWe have identified that SHOX2 expression or methylation are potent independent prognostic indicators for predicting LGG patient survival, and have potential to identify an important subset of LGG patients with IDHwt status with significantly better overall survival. The combination of IDH or other relevant markers with SHOX2 identified LGG subsets with significantly different survival outcomes, and further understanding of these subsets may benefit therapeutic target identification and therapy selections for glioma patients.

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“…In practice, univariable Cox regression analysis was applied to each variable, which was regarded to be significant considering its correlation with survival time or its distinct stratification of patients. Significant variables were selected using either Wald t -test on regression coefficients [15] or log-rank test with permutations after dividing patients into high- and low-risk groups by univariable risk-score analysis [16, 17]. A risk score of each observation was obtained using a linear combination of the expression levels of selected variables weighted by multivariable regression coefficients.…”

Section: Introductionmentioning

confidence: 99%

Joint Covariate Detection on Expression Profiles for Selecting Prognostic miRNAs in Glioblastoma

Sun

Zhao

2017

BioMed Research International

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An important application of expression profiles is to stratify patients into high-risk and low-risk groups using limited but key covariates associated with survival outcomes. Prior to that, variables considered to be associated with survival outcomes are selected. A combination of single variables, each of which is significantly related to survival outcomes, is always regarded to be candidates for posterior patient stratification. Instead of individually significant variables, a combination that contains not only significant but also insignificant variables is supposed to be concentrated on. By means of bottom-up enumeration on each pair of variables, we propose a joint covariate detection strategy to select candidates that not only correspond to close association with survival outcomes but also help to make a clear stratification of patients. Experimental results on a publicly available dataset of glioblastoma multiforme indicate that the selected pair composed of an individually significant and an insignificant miRNA keeps a better performance than the combination of significant single variables. The selected miRNA pair is ultimately regarded to be associated with the prognosis of glioblastoma multiforme by further pathway analysis.

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Prognostic Value of a Nine‐Gene Signature in Glioma Patients Based on mRNA Expression Profiling

Abstract: This 9-gene-signature prediction model provided a more accurate predictor of prognosis that denoted patients with high risk score have poor outcome. Moreover, these risk models based on defined molecular profiles showed the considerable prospect in personalized cancer management.

Cited by 85 publications

References 36 publications

Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage

Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage

SHOX2 is a Potent Independent Biomarker to Predict Survival of WHO Grade II–III Diffuse Gliomas

Joint Covariate Detection on Expression Profiles for Selecting Prognostic miRNAs in Glioblastoma

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