Dataset Information

Clinical significance of miRNA?1 and its potential target gene network in lung squamous cell carcinoma.

ABSTRACT: Previous studies demonstrated that miRNA?1 (miR?1) is downregulated in certain human cancer and serves a crucial role in the progression of cancer. However, there are only a few previous studies examining the association between miR?1 and lung squamous cell carcinoma (LUSC) and the regulatory mechanism of miR?1 in LUSC remains unclear. Therefore, the present study investigated the clinical significance and determined the potential molecular mechanism of miR?1 in LUSC. The expression of miR?1 and its clinical significance in LUSC was examined by conducting a meta?analysis of 12 studies using Stata 14, MetaDiSc1.4 and SPSS version 23. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the potential target genes of miR?1 gathered from Gene Expression Omnibus and ArrayExpress. Meta?analysis demonstrated that miR?1 was significantly downregulated in LUSC [standardized mean difference: ?1.44; 95% confidence interval (CI): ?2.08, ?0.81], and the area under the curve was 0.9096 (Q*=0.8416) with sensitivity of 0.71 (95% CI: 0.66, 0.76) and specificity of 0.88 (95% CI: 0.86, 0.90). The pooled positive likelihood ratio and negative likelihood ratio were 4.93 (95% CI: 2.54, 9.55) and 0.24 (95% CI: 0.10, 0.54), respectively. Bioinformatics analysis demonstrated that miR?1 may be involved in the progression of LUSC via the 'cell cycle', 'p53 signaling pathway', 'Fanconi anemia pathway', 'homologous recombination', 'glycine, serine and threonine metabolism' and 'oocyte meiosis'. In summary, miR?1 was significantly downregulated in LUSC, suggesting a novel and promising non?invasive biomarker for diagnosing LUSC, and miR?1 was involved in LUSC progression via a number of significant pathways.

SUBMITTER: Li X

PROVIDER: S-EPMC6522896 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Clinical significance of miRNA‑1 and its potential target gene network in lung squamous cell carcinoma.

Li Xiaojiao X Qin Meijiao M Huang Jiacheng J Ma Jie J Hu Xiaohua X

Molecular medicine reports 20190419 6

Previous studies demonstrated that miRNA‑1 (miR‑1) is downregulated in certain human cancer and serves a crucial role in the progression of cancer. However, there are only a few previous studies examining the association between miR‑1 and lung squamous cell carcinoma (LUSC) and the regulatory mechanism of miR‑1 in LUSC remains unclear. Therefore, the present study investigated the clinical significance and determined the potential molecular mechanism of miR‑1 in LUSC. The expression of miR‑1 and ...[more]

PMID: 31059033

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers.MethodsClinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC.ResultsA total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc.ConclusionSeveral collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.

Project description:Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72-1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83-0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein-protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

Dataset Information

Clinical significance of miRNA?1 and its potential target gene network in lung squamous cell carcinoma.

Publications

Clinical significance of miRNA‑1 and its potential target gene network in lung squamous cell carcinoma.

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