Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients

Szász, András; Lánczky, András; Nagy, Ádám; Förster, Susann; Kim, Hark; Green, Jeffrey E.; Boussioutas, Alex; Busuttil, Rita A.; Szabó, András; Győrffy, Balázs

doi:10.18632/oncotarget.10337

Cited by 836 publications

(757 citation statements)

References 46 publications

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“…Medians were compared using the Mann-Whitney U-test for non-normally distributed data, while means were compared using the two-sample t-test for normally distributed data. Kaplan Meier survival curves were produced from online expression databases KMplot (16) and Gene Expression Miner (17). Gene Expression Miner also used publically available expression data to produce a boxplot correlation of FST mRNA level with tumour grade.…”

Section: Methodsmentioning

confidence: 99%

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Zabkiewicz

Resaul

Hargest

et al. 2017

CGP

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Abstract. Background Follistatin (FST) is a secreted extracellular regulatory protein that binds activin and, with less affinity, related TGFβ superfamily members such as bone morphogenetic proteins (BMPs), preventing access to their receptors (1, 2). Originally thought to act on the pituitary to regulate FSH release, FST has subsequently been noted in many other tissues, in particular co-localising with activin resulting in autocrine and paracrine cellular regulation (1, 3). As an antagonist of activin, FST has diverse regulatory roles in embryogenesis, tissue differentiation and repair, gonadal function and inflammatory and immune processes (3, 4).Three major FST isoforms can be produced, namely FST288 (from splice variant mRNA precursor FST317), FST315 (from splice variant mRNA precursor FST344) and a third FST isoform, FST303, produced from the post-translational truncation of the FST315 C-terminus (5). These three main FST isoforms can also be glycosylated to yield six further FST isoforms (6). FST288 and FST315 are differentially expressed in human tissues, but FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (6, 7) .The FST/activin interaction has been implicated in tumour proliferation, angiogenesis and metastasis in several solid tumours (8-11). Activin has primarily been seen as an inhibitor of cellular proliferation, although certain cell populations seem to be stimulated by activin. Thus, the overall result of activin/FST action in cancer may be both context and cell type specific (3, 6).In the breast, FST is expressed in the normal mammary gland and in different breast proliferative diseases, with additional experimental evidence suggesting that FST can modulate the breast cancer cell cycle (3,(12)(13)(14). However, its role in breast cancer growth and metastasis is far from clear. In this study we demonstrated a clinical correlation between FST expression and survival in breast cancer, and that overexpression of FST in vitro reduces invasion of breast cancer cells. Patients and MethodsCell lines and patient tissue samples. Human breast cell lines MCF-7,MDA MB 231, ZR-751, BT 549 and BT-20 were obtained from and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% foetal calf serum and antibiotics (PAA Laboratories Ltd., Somerset, UK). Cells were incubated at 37˚C in 5% CO 2 at 95% humidity.Breast cancer tissue and normal breast tissue samples were collected during surgery at the University Hospital of Wales. In total, 93 tumour samples and 30 normal breast tissue samples were obtained from patients who were enrolled in the study. The tissues obtained during surgery were snap-frozen in liquid nitrogen and stored at −80˚C.

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Section: Methodsmentioning

confidence: 99%

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Zabkiewicz

Resaul

Hargest

et al. 2017

CGP

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“…Therefore, a promising potential is indicated for FST in HCC prognosis. A survival analysis of FST in breast, lung, ovarian and gastric cancer was also performed using an online Kaplan-Meier analysis (http://kmplot.com/analysis/) (Figure 1) (107). An increased expression of FST was associated with poorer overall survival of patients with ovarian, gastric and lung cancer.…”

Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 99%

“…OS: Overall survival; RFS: relapse-free survival. The association with survival of patients with ovarian, breast, lung and gastric cancer was analysed in a combined cohort of these cancer types using an online Kaplan-Meier survival analysis tool (KMplot, http://kmplot.com/analysis/) (107). Numbers of patients of each cohort and the cut-off levels which were auto-selected using the KMplot are shown.…”

Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 99%

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi

Resaul

Owen

et al. 2016

CGP

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Abstract. Follistatin (FST) Follistatin (FST), which was first isolated from porcine and bovine follicular fluid (1, 2), was initially described as a protein involved in the regulation of the secretion of folliclestimulating hormone. This monomeric glycosylated polypeptide chain is encoded by a single gene located on the long arm chromosome 5q11.2 (3), which through alternative splicing may be transcribed into the mRNA precursors, FST317 and FST344. From these precursors, three major FST isoforms may be produced, namely FST288 (from pre-FST317), FST315 (from pre-FST344) and a third FST isoform, FST303, produced from the post-translational truncation of the FST315 C-terminus. These three main FST isoforms can also be glycosylated to yield six further FST isoforms that were previously identified in bovine (4) and porcine (5, 6) follicular fluid. At the core, all FST isoforms contain a 63 residue N-terminal domain and three follistatin domains, termed FSD1, FSD2 and FSD3. These domains comprise 73-77 amino acid residues and are characterised by an arrangement of 10 conserved cysteine residues (7). Both FST288 and FST315 are differentially expressed in human tissues (6-9). FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (10, 11). Some molecules such as activin, transforming growth factor-beta (TGFβ), forkhead domain transcription factor L2 (12, 13), gonadotropin-releasing hormone (14), zinc finger protein (GLI2) (15), dexamethasone (16), androgens (17), activators of winglessrelated integration site (WNT) signalling (18, 19) and 1,25-dihydroxyvitamin D (20) have been shown to regulate the transcription of the FST gene. In addition, down-regulation of FST gene expression by peroxisome proliferator-activated receptor gamma (PPARγ) or the transcription factor epiprofin (21, 22) has been shown.As an antagonist of TGFβ superfamily member activin, FST seems to primarily function in relation to the role that activin plays. Along with FST, activin acts as a pleiotropic growth factor system, which is involved in proliferation, differentiation, and apoptosis of a number of cell types (23-28). As such, the functions of the FST isoforms are therefore linked to their binding affinity for activin (6,10,11,(29)(30)(31)(32)(33)(34)(35)(36)(37). In fact, this critical binding and neutralisation of activin, either partial or complete, is based on the order of at least two of the FST cysteine domains and its Nterminal (38), conferring a difference in affinities for activin between the FST isoforms. The binding complex between activin and FST generally occurs in a 1:2 ratio, where the two FST molecules, connected C-terminus to N-425

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“…Multiple public resources such as Wanderer [9], METHHC [10] and MEXPRESS [11] provide a simple user interface to explore the relationship between methylation and gene expression data originating from TCGA. Additionally, tools to perform survival analysis using gene expression data from TCGA are also available to the research community [12][13][14][15][16][17][18][19][20]. However, there are no tools to facilitate the evaluation of the prognostic properties of CpG methylation data.…”

Section: Introductionmentioning

confidence: 99%

MethSurv: A Web Tool to Perform Multivariable Survival Analysis Using DNA Methylation Data

et al. 2017

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Aim:To develop a web tool for survival analysis based on CpG methylation patterns. Materials & methods: We utilized methylome data from 'The Cancer Genome Atlas' and used the Cox proportional-hazards model to develop an interactive web interface for survival analysis. Results: MethSurv enables survival analysis for a CpG located in or around the proximity of a query gene. For further mining, cluster analysis for a query gene to associate methylation patterns with clinical characteristics and browsing of top biomarkers for each cancer type are provided. MethSurv includes 7358 methylomes from 25 different human cancers. Conclusion: The MethSurv tool is a valuable platform for the researchers without programming skills to perform the initial assessment of methylation-based cancer biomarkers.

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Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients

Cited by 836 publications

References 46 publications

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

MethSurv: A Web Tool to Perform Multivariable Survival Analysis Using DNA Methylation Data

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