An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients

Győrffy, Balázs; Lánczky, András; Eklund, Aron C.; Denkert, Carsten; Budczies, Jan; Li, Qiyuan; Szállási, Zoltán

doi:10.1007/s10549-009-0674-9

Cited by 3,361 publications

(3,857 citation statements)

References 33 publications

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“…Computational analysis using the KM plotter integrative bioinformatic interface 24 revealed a significant correlation between high FOSL1 mRNA expression and poor metastasis-free survival (Figure 1a). This correlation extended to overall survival ( Figure 1b) and was unique among Fos genes as the inverse trend was obtained when stratifying this very large cohort (1609 and 1105 patients, respectively) according to the expression of FOS (Figures 1c and d), FOSL2 or FOSB (Supplementary Figure S1).…”

Section: Resultsmentioning

confidence: 99%

Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression

et al. 2014

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Epithelial-to-mesenchymal transition (EMT) is essential for embryonic morphogenesis and wound healing and critical for tumour cell invasion and dissemination. The AP-1 transcription factor Fra-1 has been implicated in tumorigenesis and in tumour-associated EMT in human breast cancer. We observed a significant inverse correlation between Fra-1 mRNA expression and distant-metastasis-free survival in a large cohort of breast cancer patients derived from multiple array data sets. This unique correlation among Fos genes prompted us to assess the evolutionary conservation between Fra-1 functions in EMT of human and mouse cells. Ectopic expression of Fra-1 in fully polarized, non-tumourigenic, mouse mammary epithelial EpH4 cells induced a mesenchymal phenotype, characterized by a loss of epithelial and gain of mesenchymal markers. Proliferation, motility and invasiveness were also increased in the resulting EpFra1 cells, and the cells were tumourigenic and efficiently colonized the lung upon transplantation. Molecular analyses revealed increased expression of Tgfβ1 and the EMT-inducing transcription factors Zeb1, Zeb2 and Slug. Mechanistically, Fra-1 binds to the tgfb1 and zeb2 promoters and to an evolutionarily conserved region in the first intron of zeb1. Furthermore, increased activity of a zeb2 promoter reporter was detected in EpFra1 cells and shown to depend on AP-1-binding sites. Inhibiting TGFβ signalling in EpFra1 cells moderately increased the expression of epithelial markers, whereas silencing of zeb1 or zeb2 restored the epithelial phenotype and decreased migration in vitro and tumorigenesis in vivo. Thus Fra-1 induces changes in the expression of genes encoding EMT-related transcription factors leading to the acquisition of mesenchymal, invasive and tumorigenic capacities by epithelial cells. This study defines a novel function of Fra-1/AP-1 in modulating tgfb1, zeb1 and zeb2 expression through direct binding to genomic regulatory regions, which establishes a basis for future in vivo genetic manipulations and preclinical studies using mouse models. Epithelial-to-mesenchymal transition (EMT) is a complex biological programme that occurs in physiological processes during embryonic development and wound healing as well as in pathological conditions, such as organ fibrosis and carcinogenesis. During EMT, cells lose epithelial features and acquire mesenchymal characteristics. The acquisition of a mesenchymal state by malignant cancer cells is associated with decreased cell-cell adhesion, and increased migratory and invasive properties, which are crucial for metastasis. [1][2][3][4][5] The adherens junction (AJ) protein E-cadherin, encoded by cdh1, is a central determinant of the epithelial state and its downregulation is the hallmark of EMT. A number of molecular pathways converging on E-cadherin have been implicated in EMT. Transcription factors (TF) of the Snail, Zeb and Twist families, initially identified as regulators of epithelialmesenchymal plasticity during morphogenesis were shown to orchestrate EMT by...

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Section: Resultsmentioning

confidence: 99%

Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression

et al. 2014

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“…21 The following genes that may play a role in breast cancer 10‐year relapse free survival (RFS) were assessed SPHK1 (219257_s_at), SPHK2 (209857_s_at), SGPP1 (208381_s_at), SGPP2 (226560_at), LPP1 (210946_at), LPP2 (209529_at), LPP3 (212230_at), SGPL 1 (223391_at), S1PR 1 (204642_at), S1PR 2 (208537_at), S1PR 3 (228176_at), S1PR 4 (206437_at), and S1PR 5 (221417_x_at). Databases of the following cohorts were analyzed: nonclassified BCA (n = 1660); ER +/− (n = 695/313); PR +/− (n = 489/372); HER2 +/− (n = 150/635); lymph node metastasis positive and negative (n = 724/496); grade 1, grade 2, and 3 (n = 108/227/444); and intrinsic subtypes including basal (n = 339), luminal A (n = 841), and luminal B (n = 407): Tp53 mutant or wild type (n = 132/82); with systemically treatment (n = 751); include or exclude endocrine therapy or Tamoxifen only (n = 335/275/161); and with or without chemotherapy (n = 255/243).…”

Section: Methodsmentioning

confidence: 99%

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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“…To illustrate this point, we plotted the KaplanMeier recurrence-free survival curves for CD73 (Affymetrix ID: 203939_at) in www.kmplot.com. This recently developed web-based tool, which plots Kaplan-Meir survival curves for any of the 22,277 probe sets represented on Affymetrix gene chips (40). The tool is based on public microarray data from breast cancer patients and allows for filtering by hormone receptor status, nodal status, and adjuvant endocrine treatment.…”

Section: Kaplan-meier Plotter Online Survival Analysismentioning

confidence: 99%

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

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SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

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An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients

Cited by 3,361 publications

References 33 publications

Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression

Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

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