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Integrative analysis of miRNA and mRNA expression profiles reveals a novel mRNA/miRNA signature to improve risk classification for patients with gastric cancer.

ABSTRACT: Gastric cancer (GC) is one of the most common types of malignant cancer and is associated with poor prognosis. Although the prognosis of patients with GC is associated with grade, stage and lymph node metastases, these traditional clinical features are inadequate to predict the outcome of GC. Therefore, there has been an increased focus on identifying novel molecular biomarkers for early diagnosis and prognosis, in order to improve outcomes in GC. In the present study, an integrative analysis of microRNA (miRNA) expression profiles, mRNA expression profiles and clinical characteristics was performed in a large cohort of patients with GC in order to identify an integrative prognostic model for improving postoperative risk classification. An integrative mRNA/miRNA signature (IMMIS), comprised of three miRNAs and one mRNA, was identified from a large number of differentially expressed miRNAs and mRNAs using univariate and multivariate Cox regression analysis. The prognostic value of the IMMIS was validated in the discovery cohort, testing cohort and The Cancer Genome Atlas (TCGA) cohort. The present results suggested that the identified signature had a reliable predictive performance and could classify the patients into high- and low-risk groups with significantly different overall survival times. In the discovery cohort, the hazard ratio (HR) was 2.805 with a 95% CI=1.722-4.567 (P<0.001). The median overall survival time as 1.49 vs. 3.85 years. In the testing cohort, the HR was 1.625 with a 95% CI=1.004-2.638 (P=0.039) and the median overall survival time was 2.17 vs. 4.62 years. In the TCGA cohort, the HR was 2.139 with a 95% CI=1.519-3.012 (P<0.001) and the median overall survival time was 1.53 vs. 4.62 years. The IMMIS constituted a reliable independent prognostic factor compared with clinical covariates, including age, sex, grade and stage, as indicated by multivariate and stratified analyses. Furthermore, comparative analysis revealed that the predictive value of the IMMIS was superior to the mRNA-based signature alone. The present results suggested the potential value of the IMMIS as a promising novel biomarker for improving the clinical management of patients with GC.

SUBMITTER: Yin X

PROVIDER: S-EPMC6676680 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Integrative analysis of miRNA and mRNA expression profiles reveals a novel mRNA/miRNA signature to improve risk classification for patients with gastric cancer.

Yin Xiang X Zhang Fumin F Guo Zhongwu Z Kong Weiyuan W Wang Yuanyuan Y

Oncology letters 20190627 3

Gastric cancer (GC) is one of the most common types of malignant cancer and is associated with poor prognosis. Although the prognosis of patients with GC is associated with grade, stage and lymph node metastases, these traditional clinical features are inadequate to predict the outcome of GC. Therefore, there has been an increased focus on identifying novel molecular biomarkers for early diagnosis and prognosis, in order to improve outcomes in GC. In the present study, an integrative analysis of ...[more]

PMID: 31402938

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Project description:BackgroundStromal cells play an important role in the process of tumor progression, but the relationship between stromal cells and metabolic reprogramming is not very clear in gastric cancer (GC).MethodsMetabolism-related genes associated with stromal cells were identified in The Cancer Genome Atlas (TCGA) and GSE84437 datasets, and the two datasets with 804 GC patients were integrated into a training cohort to establish the prognostic signature. Univariate Cox regression analysis was used to screen for prognosis-related genes. A risk score was constructed by LASSO regression analysis combined with multivariate Cox regression analysis. The patients were classified into groups with high and low risk according to the median value. Two independent cohorts, GSE62254 (n = 300) and GSE15459 (n = 191), were used to externally verify the risk score performance. The CIBERSORT method was applied to quantify the immune cell infiltration of all included samples.ResultsA risk score consisting of 24 metabolic genes showed good performance in predicting the overall survival (OS) of GC patients in both the training (TCGA and GSE84437) and testing cohorts (GSE62254 and GSE15459). As the risk score increased, the patients' risk of death increased. The risk score was an independent prognostic indicator in both the training and testing cohorts suggested by the univariate and multivariate Cox regression analyses. The patients were clustered into four subtypes according to the quantification of 22 kinds of immune cell infiltration (ICI). The proportion of ICI Cluster C with the best prognosis in the low-risk group was approximately twice as high as that in the high-risk group, and the risk score of ICI Cluster C was significantly lower than that of the other three subtypes.ConclusionOur study proposed the first scheme for prognostic risk classification of GC from the perspective of tumor stromal cells and metabolic reprogramming, which may contribute to the development of therapeutic strategies for GC.

Project description:BackgroundExcessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality, feed utilization, and reproduction. Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes, which involves a cascade of regulatory molecules. Accumulating evidence has shown that microRNAs (miRNAs) serve as post-transcriptional regulators of adipogenic differentiation in mammals. However, the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood. This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal adipogenesis.ResultsWe established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation (0, 12, 48, 72, and 120 h). A total of 217 differentially expressed miRNAs (DE-miRNAs) and 3520 differentially expressed genes were identified. Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways, including the PPAR signaling and MAPK signaling pathways. A candidate miRNA, gga-miR-106-5p, exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens. gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes. A dual-luciferase reporter assay suggested that the KLF15 gene, which encodes a transcriptional factor, is a direct target of gga-miR-106-5p. gga-miR-106-5p suppressed the post-transcriptional activity of KLF15, which is an activator of abdominal preadipocyte proliferation and differentiation, as determined with gain- and loss-of-function experiments.Conclusionsgga-miR-106-5p functions as an inhibitor of abdominal adipogenesis by targeting the KLF15 gene in chickens. These findings not only improve our understanding of the specific functions of miRNAs in avian adipogenesis but also provide potential targets for the genetic improvement of excessive abdominal fat deposition in poultry.

Dataset Information

Integrative analysis of miRNA and mRNA expression profiles reveals a novel mRNA/miRNA signature to improve risk classification for patients with gastric cancer.

Publications

Integrative analysis of miRNA and mRNA expression profiles reveals a novel mRNA/miRNA signature to improve risk classification for patients with gastric cancer.

Similar Datasets

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