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Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer.

ABSTRACT: MicroRNAs (miRNAs/miRs) regulate the expression of target genes and are considered to be associated with human cancer. The aim of the present study was to screen novel miRNA biomarkers in esophageal cancer (EC). The miRNA expression profile GSE41268 was extracted from Gene Expression Omnibus database, and differentially expressed miRNAs between whole saliva samples from patients with EC and healthy controls were identified using the Linear Models for Microarray Data package. Then, the targets of these miRNAs were screened using the miRecords database and used to construct the regulatory network. Gene ontology and pathway enrichment analyses were performed for the target genes of differentially expressed miRNAs to predict their potential functions. A total of 18 differentially expressed miRNAs were identified in saliva samples from patients with EC, and 43 validated target genes corresponding to 7 upregulated miRNAs were identified. Then, 6 miRNAs (miR-144, miR-451, miR-98, miR-10b, miR-486-5p and miR-363) and their target genes were used to construct a regulatory network. Within the network, miR-144 may target Notch homolog 1, fibrinogen α chain and fibrinogen β chain; miR-451 may regulate murine thymoma viral oncogene homolog 1, matrix metalloproteinase (MMP)9 and MMP2; miR-98 may directly target E2F transcription factor (E2F) 1, E2F2 and v-myc avian myelocytomatosis viral oncogene homolog (MYC); miR-10b may modulate peroxisome proliferator-activated receptor α and Kruppel-like factor 4; miR-485-5p and miR-363 may regulate TNF receptor superfamily member 5 and cyclin-dependent kinase inhibitor 1A. In addition, E2F1, E2F2 and MYC were associated with the cell cycle, which was the most significantly enriched function and pathway in EC. The results of the present study suggested that miR-144, miR-451, miR-98, miR-10b and miR-363 may be involved in EC by regulating their target genes, and may be used as biomarkers for EC.

SUBMITTER: Du J

PROVIDER: S-EPMC5529882 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Background Small cell lung cancer (SCLC) is an aggressive and recalcitrant cancer. In recent years, studies focused on the abnormal expression of microRNA which has proven valuable in terms of prognosis, diagnosis and treatment in SCLC. To address the limitations of independent studies data, a meta-analysis seems necessary for further exploration of microRNA as biological target and regulatory factor in SCLC. Methods We performed comprehensive literature retrieval in GEO database and EBI ArrayExpress database. The microRNA expression data was extracted from 4 related researches (GSE15008, GSE74190, GSE19945, GSE77380), which was obtained from GEO database. In each included study, the R. Affymetrix Expression Console’s Limma package and RMA algorithms were used to screen for raw data for gene chip quality control, standardization, log2 conversion and differential expression of the gene chip, respectively. Significant microRNA meta-signatures were identified by Robust Rank Aggregation method. Subsequently, gene ontology (GO) enrichment analysis and pathway analysis were performed using bioinformatics tools. Results We found a significant microRNA meta-signature of six up-regulated (hsa-miR-182-5p, hsa-miR-96-5p, hsa-miR-7-5p, hsa-miR-301b-3p, hsa-miR-130b-3p, hsa-miR-210-3p) and four down-regulated (hsa-miR-126-3p, hsa-miR-451a, hsa-miR-145-5p, hsa-miR-486-5p) microRNA s in meta-analysis approaches. GO analysis showed that target gene of meta-signatures microRNA was mainly enriched in endosome, chordate embryonic development and transforming growth factor beta receptor. The related functional gene of microRNA meta signature synergistically targeting SCLC signaling pathway was confirmed by enrichment analysis. In particular, neurotrophin and TGF-beta signaling pathway play the most important roles in the pathway network. Conclusions Our study identified 10 highly significant and consistently dysregulated microRNA s from 4 datasets, which offering convincing molecular targets and regulatory factors in future research of SCLC.

Project description:Neo-chemoradiotherapy (nCRT) before surgery is a standard treatment for locally advanced esophageal cancers. However, the treatment outcome of nCRT varied with different patients. This study aimed to identify potential biomarkers for prediction of nCRT-response in patients with esophageal squamous cell carcinoma (ESCC). Microarray datasets of nCRT responder and non-responder samples (access number GSE45670 and GSE59974) of patients with ESCC were downloaded from Gene Expression Omnibus (GEO) database. The mRNA expression profiles of cancer biopsies from four ESCC patients were analyzed before and after nCRT. Differentially expressed genes (DEGs) and miRNAs were screened between nCRT responder and non-responder ESCC samples. Functional enrichment analysis was conducted for these DEGs followed by construction of protein-protein interaction (PPI) network and miRNA-mRNA regulatory network. Finally, univariate survival analysis was performed to identify candidate biomarkers with prognostic values in ESCC. We identified numerous DEGs and differentially expressed miRNAs from nCRT responder group. GO and KEGG analysis showed that the dysregulated genes were mainly involved in biological processes and pathways, including "response to stimulus", "cellular response to organic substance", "regulation of signal transduction", "AGE-RAGE signaling pathway in diabetic complications", and "steroid hormone biosynthesis". After integration of PPI network and miRNA-mRNA network analysis, we found eight genes, TNF, AKR1C1, AKR1C2, ICAM1, GPR68, GNB4, SERPINE1 and MMP12, could be candidate genes associated with disease progression. Univariate cox regression analysis showed that there was no significant correlation between dysregulated miRNAs (such as hsa-miR-34b-3p, hsa-miR-127-5p, hsa-miR-144-3p, and hsa-miR-486-5p, et al.) and overall survival of ESCC patients. Moreover, abnormal expression of MMP12 was significantly correlated with pathological degree, TNM stage, lymph nodes metastasis, and overall survival of ESCC patients (p < 0.05). Taken together, our study identified that MMP12 might be a useful tumor biomarker and therapeutic target for ESCC.

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Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer.

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