SynTarget: an online tool to test the synergetic effect of genes on survival outcome in cancer

Amelio, Ivano; Tsvetkov, Philipp O.; Knight, Richard; Lisitsa, Andrey; Melino, Gerry; Antonov, A V

doi:10.1038/cdd.2016.12

Cited by 38 publications

(40 citation statements)

References 8 publications

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“…These results were further corroborated by our bioinformatics analysis [15,16] (Fig. 3G), where we used publically available datasets and found that high levels of ACTN4 expression correlated with negative outcome for patients with lung adenocarcinoma (p-value 0.00113).…”

Section: Actn4 Overexpression Enhances H1299 Proliferation But Blockssupporting

confidence: 68%

Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells

et al. 2017

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Alpha-actinin 4 (ACTN4) is an actin-binding protein of the spectrin superfamily. ACTN4 is found both in the cytoplasm and nucleus of eukaryotic cells. The main function of cytoplasmic ACTN4 is stabilization of actin filaments and their binding to focal contacts. Nuclear ACTN4 takes part in the regulation of gene expression following by activation of certain transcription factors, but the mechanisms of regulation are not completely understood. Our previous studies have demonstrated the interaction of ACTN4 with the RelA/p65 subunit of NF-kappaB factor and the effect on its transcriptional activity in A431 and HEK293T cells. In the present work, we investigated changes in the composition of nuclear ACTN4-interacting proteins in non-small cell lung cancer cells H1299 upon stable RELA overexpression. We showed that ACTN4 was present in the nuclei of H1299 cells, regardless of the RELA expression level. The presence of ectopic RelA/p65 in H1299 cells increased the number of proteins interacting with nuclear ACTN4. Stable expression of RELA in these cells suppressed cell proliferation, which was further affected by simultaneous ACTN4 overexpression. We detected no significant effect on cell cycle but the apoptosis rate was increased in cells with a double RELA/ACTN4 overexpression. Interestingly, when expressed individually ACTN4 promoted proliferation of lung cancer cells. Furthermore, the bioinformatics analysis of gene expression in lung cancer patients suggested that overexpression of ACTN4 correlated with poor survival prognosis. We hypothesize that the effect of RELA on proliferation and apoptosis of H1299 cells can be mediated via affecting the interactome of ACTN4.

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Section: Actn4 Overexpression Enhances H1299 Proliferation But Blockssupporting

confidence: 68%

Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells

et al. 2017

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“…Our results from TCGA mirror findings from SynTarget, a new online tool that interrogates the expression of multiples genes from microarray data sets for synergistic survival relationships [22, 23]. We utilized this tool to assess the synergistic relationships between Ang2, Tie2 and VEGFA within two breast cancer microarray data sets provided by SynTarget.…”

Section: Discussionmentioning

confidence: 59%

“…In agreement with the relationships identified using RNA-seq data from TCGA, SynTarget identified decreased survival in those with high Ang2 expression (Supplementary Figure 3a). Similarly, those with combined low Ang2 expression and high Tie2 expression saw increased survival (Supplementary Figure 3b) [22, 23]. Additionally, SynTarget reported decreased survival with high Ang2 and high VEGFA expression, and improved survival with low Ang2 and low VEGFA expression (Supplementary Figure 3c and 3d).…”

Section: Discussionmentioning

confidence: 92%

Angiopoietin pathway gene expression associated with poor breast cancer survival

Ramanathan

Olex

Dozmorov

et al. 2017

Breast Cancer Res Treat

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Purpose Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a “big data” approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA). Methods A total of 888 patients with adequate gene expression, disease-free survival (DFS) and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated. Results The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology and survival. High Ang2 gene expression was associated with not only decreased DFS (p=0.05), but also decreased OS (p<0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p<0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS. Conclusions This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data supports the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.

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“…A total of 156 tumor samples and 5 normal paired normal sample were included in the RRM2 expression comparison. To evaluate the relationship between RRM2 expression and survival of GBM patients, Kaplan-Meier survival curve (overall) was analyzed using the SynTarget/BioProfiling database [24] for the TCGA_GBM dataset (121 patient samples).…”

Section: Data Acquisition From Tcga (The Cancer Genome Atlas) and Surmentioning

confidence: 99%

“…Here, we analyzed the relationship between RRM2 expression and the survival of GBM patients. Survival data were retrieved from SynTarget/BioProfiling database (TCGA_GBM) [24]. Patients with higher RRM2 expression rank than the average RRM2 expression rank across the TCGA_GBM dataset were classified as the high RRM2 group (52 cases), and the others were in the low RRM2 group (69 cases).…”

Section: Rrm2 Expression Is Enhanced In Human Glioma Tissuesmentioning

confidence: 99%

RRM2 is a potential prognostic biomarker with functional significance in glioma

Sun¹,

Yang²,

Zhang³

et al. 2019

Int. J. Biol. Sci.

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Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

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SynTarget: an online tool to test the synergetic effect of genes on survival outcome in cancer

Cited by 38 publications

References 8 publications

Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells

Co-expression of RelA/p65 and ACTN4 induces apoptosis in non-small lung carcinoma cells

Angiopoietin pathway gene expression associated with poor breast cancer survival

RRM2 is a potential prognostic biomarker with functional significance in glioma

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