Four microRNAs Signature for Survival Prognosis in Colon Cancer using TCGA Data

Xu, Jian; Zhao, Jian; Zhang, Rui

doi:10.1038/srep38306

Cited by 27 publications

(25 citation statements)

References 21 publications

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“…34,41 Receiver operator curve (ROC) analyses were also used as in Ref. 42 using FEV 1 less than 80% predicted or taking more than or equal to 1000 μg/day inhaled steroid and gave a similar cut-point (42 993 pg/mL; FEV 1 : Sen = 0.77, Spec = 0.77; Inhaled Steroid: Sen = 0.8, Spec = 0.62). Stratified data were analyzed for statistical significance using Pearson's the χ 2 test for categorical data and independent t test for continuous variables.…”

Section: Discussionmentioning

confidence: 99%

“…Patients were stratified by median IL‐2 (42 600 pg/mL) as in Refs . Receiver operator curve (ROC) analyses were also used as in Ref . using FEV 1 less than 80% predicted or taking more than or equal to 1000 μg/day inhaled steroid and gave a similar cut‐point (42 993 pg/mL; FEV 1 : Sen = 0.77, Spec = 0.77; Inhaled Steroid: Sen = 0.8, Spec = 0.62).…”

Section: Methodsmentioning

confidence: 99%

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IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

Kanagalingam

Solomon

Vijeyakumaran

et al. 2019

Immunity Inflam & Disease

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Background Glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine expression and induce apoptosis. Asthma severity is associated with type 2 inflammation, circulating Th2 cells and higher GC requirements. Objective The aim of this study was to assess whether ex vivo production of interleukin 2 (IL‐2), a T‐cell survival factor, associated with clinical features of asthma severity, the proportion of blood Th2 cells and Th2 cell responses to GC. Methods Peripheral blood from asthma patients (n = 18) was obtained and the proportion of Th2 cells determined by flow cytometry. Peripheral blood cells were activated with mitogen (24 hours) and supernatant levels of IL‐2 and IL‐13 measured by enzyme‐linked immunosorbent assay. In vitro differentiated Th2 cells were treated with dexamethasone (DEX) and IL‐2 and assessed for apoptosis by flow cytometry (annexin V). Level of messenger RNA (mRNA) for antiapoptotic (BCL‐2) and proapoptotic (BIM) genes, IL‐13, GC receptor (GR) and FKBP5 were determined by quantitative real‐time polymerase chain reaction. GR binding was assessed by chromatin immunoprecipitation. Results IL‐2 produced by activated peripheral blood cells correlated negatively with lung function and positively with a daily dose of inhaled GC. When patients were stratified based on IL‐2 level, high IL‐2 producers made more IL‐13 and had a higher proportion of circulating Th2 cells. In vitro, increasing the level of IL‐2 in the culture media was associated with resistance to DEX‐induced apoptosis, with more BCL‐2/less BIM mRNA. Th2 cells cultured in high IL‐2 had more IL‐13, less GR mRNA, showed reduced binding of the GR to FKBP5, a known GC‐induced gene, and required higher concentrations of DEX for cytokine suppression. Conclusions and Clinical Relevance IL‐2 downregulates Th2 cell responses to GC, supporting both their survival and pro‐inflammatory capacity. These results suggest that a patient's potential to produce IL‐2 may be a determinant in asthma severity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

Kanagalingam

Solomon

Vijeyakumaran

et al. 2019

Immunity Inflam & Disease

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“…Thus, the exploration of powerful markers which may provide prognostic value for cholangiocarcinoma patients is of great significance. Currently, prognostic microRNA (miRNA) expression signatures in various cancers, such as colon cancer (7), clear cell renal cell carcinoma (8) and cervical cancer (9) have attracted the attention of researchers. Therefore, the miRNA signature has been regarded as an important change in cholangiocarcinoma progression and therapy (10).…”

Section: Introductionmentioning

confidence: 99%

A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data

Cao

Sun

et al. 2018

Oncol Rep

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Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor progression and metastasis. These miRNAs may serve as prognostic biomarkers and potential therapeutic targets. The aim of the present study was to identify the differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues by analyzing high‑throughput data derived from The Cancer Genome Atlas (TCGA) database. Furthermore, we evaluated the prognostic performance of the differentially expressed miRNAs and developed a novel three‑miRNA signature which predicted survival in cholangiocarcinoma patients. According to the cut‑off criteria of P<0.01 and |log2FC|>1.0, a total of 100 miRNAs (54 upregulated and 46 downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100 miRNAs, we obtained three miRNAs (miR‑10b, miR‑22 and miR‑551b) which were markedly related to patient overall survival (OS). Subsequently, a novel three‑miRNA signature was established and validated to be effective to predict survival. The results demonstrated that the survival rate, as well as the survival time of patients were obviously enhanced in relation to a lower miRNA signature index. Univariate and multivariate Cox regression analyses revealed that the three‑miRNA signature was an independent prognostic factor in cholangiocarcinoma. The reliability of the three‑miRNA signature was validated by an independent cohort from Gene Expression Omnibus (GEO). Furthermore, the functional enrichment analysis emphasized that the target genes of the aforementioned miRNAs may be involved in a variety of pathways and processes associated with cancer. Finally, these three miRNAs were detected for verification of expression using RT‑qPCR, and miR‑551b was selected for the verification of biological functions in cholangiocarcinoma cells. The results revealed that overexpression of miR‑551b decreased cancer cell proliferation and promoted apoptosis. Collectively, the results of the present study indicated that a specific three‑miRNA signature could be considered as an alternative prognostic marker in cholangiocarcinoma.

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“…In agreement with our findings, similar studies have already been carried out for the identification of prognostic miRNA signatures from the TCGA in other types of cancers, including bladder cancer, glioblastoma, colon cancer, etc. (Gonzalez-Vallinas et al, 2018;Hermansen et al, 2017;Liu et al, 2017a;Wong et al, 2016;Xu et al, 2016;Zhou et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

Yang

Zhao

et al. 2018

Molecular Oncology

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The current tumor node metastasis (TNM) staging system is inadequate for identifying high‐risk gastric cancer (GC) patients. Using a systematic and comprehensive‐biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)‐recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11‐miRNA signature that could successfully discriminate high‐risk patients in the training set (n = 372; P < 0.0001). Quantitative real‐time polymerase chain reaction‐based validation in an independent clinical cohort (n = 88) of formalin‐fixed paraffin‐embedded clinical GC samples showed that MRC‐derived high‐risk patients succumb to significantly poor recurrence‐free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time‐dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical‐related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA‐based signature is superior to currently used clinicopathological features for identifying high‐risk GC patients. It can be readily translated into clinical practice with formalin‐fixed paraffin‐embedded specimens for specific decision‐making applications.

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Four microRNAs Signature for Survival Prognosis in Colon Cancer using TCGA Data

Cited by 27 publications

References 21 publications

IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

IL‐2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?

A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

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