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Identification of differentially expressed miRNAs in BM+ vs. BM- lung cancer samples

ABSTRACT: Brain metastasis (BM) can affect up to 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been fairly disappointing. Small non-coding microRNAs (miRNAs) regulate the expression of target mRNAs by repressing their translation or regulating their sequence-specific degradation. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which makes them a powerful tool to be exploited for early detection of disease, risk assessment, and prognosis. In this study, we investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from patients with BM (BM+) and without BM (BM-). miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. Gene expression analysis comparing NSCLC parental and stably transfected miR-328 cells identified several significantly differentially-expressed genes, whose expression may be directly or indirectly regulated by miR-328. NSCLC Cell Line A549 analysis: Two-condition experiment, A549 GFP Control vs. A549 miR-328 cells. Biological replicates: 2 control replicates, 2 miR-328 replicates. miRNA microarray analysis was performed on RNA extracted from formalin-fixed paraffin-embedded (FFPE) NSCLC tumor specimens from 7 BM+ patients and 5 BM- patients.

ORGANISM(S): Homo sapiens

SUBMITTER: Ross Julianna

PROVIDER: S-ECPF-GEOD-23019 | biostudies-other |

REPOSITORIES: biostudies-other

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Identification of differentially expressed miRNAs in BM+ vs. BM- lung cancer samples

Project description:Brain metastasis (BM) can affect up to 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been fairly disappointing. Small non-coding microRNAs (miRNAs) regulate the expression of target mRNAs by repressing their translation or regulating their sequence-specific degradation. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which makes them a powerful tool to be exploited for early detection of disease, risk assessment, and prognosis. In this study, we investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from patients with BM (BM+) and without BM (BM-). miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. Gene expression analysis comparing NSCLC parental and stably transfected miR-328 cells identified several significantly differentially-expressed genes, whose expression may be directly or indirectly regulated by miR-328.

2011-02-16 | GSE23019 | GEO

Identification of differentially expressed miRNAs in BM+ vs. BM- lung cancer samples

2011-02-16 | E-GEOD-23019 | biostudies-arrayexpress

Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

Project description:Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy. miRNA microarray was performed on RNA extracted from matched human serum or plasma obtained from NSCLC patients

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Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

2012-12-01 | GSE25019 | GEO

Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

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Identification of differentially expressed miRNAs and miRNA-targeted genes in bladder cancer.

Project description:BackgroundDifferentially expressed genes and their post-transcriptional regulator-microRNAs (miRNAs), are potential keys to pioneering cancer diagnosis and treatment. The aim of this study was to investigate how the miRNA-mRNA interactions might affect the tumorigenesis of bladder cancer (BC) and to identify specific miRNA and mRNA genetic markers in the two BC types: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).ResultsWe identified 227 genes that interacted with 54 miRNAs in NMIBC, and 14 genes that interacted with 10 miRNAs in MIBC. Based on this data, we found extracellular matrix-related genes are highly enriched in NMIBC while genes related to core nuclear division are highly enriched in MIBC. Furthermore, using a transcriptional regulatory element database, we found indirect regulatory transcription factors (TFs) for enriched genes could regulate tumorigenesis with or without miRNAs.Materials and methodsTissue samples from 234 patients histologically diagnosed with BC and 83 individuals without BC were analyzed using microarray and next-generation sequencing technology, and we used different cut-offs to identify differentially expressed mRNAs and miRNAs in NMIBC and MIBC. The selected mRNAs and miRNAs were paired using validated target datasets and according to inverse expression relationships. MiRNA interacted genes were compared with the TF-regulating genes in BC. Meanwhile, pathway enrichment analysis was performed to identify the functions of selected miRNAs and genes.ConclusionsIdentification of differential gene expression in specific tumor types could facilitate development of cancer diagnosis and aid in the early detection of BC.

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Identification of differentially expressed RNAs of lung cancer cells

Project description:Twist1 induces cancer metastasis. Identification of Twist1 downstream targets should help to delineate the mechanisms of Twist1-induced cancer metastasis. Expression profiles of H1299 control cells vs. H1299 with knockdown of Twist1 were compared to identify Twist1 downstream targets.

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Rough sets for in silico identification of differentially expressed miRNAs.

Project description:The microRNAs, also known as miRNAs, are the class of small noncoding RNAs. They repress the expression of a gene posttranscriptionally. In effect, they regulate expression of a gene or protein. It has been observed that they play an important role in various cellular processes and thus help in carrying out normal functioning of a cell. However, dysregulation of miRNAs is found to be a major cause of a disease. Various studies have also shown the role of miRNAs in cancer and the utility of miRNAs for the diagnosis of cancer and other diseases. Unlike with mRNAs, a modest number of miRNAs might be sufficient to classify human cancers. However, the absence of a robust method to identify differentially expressed miRNAs makes this an open problem. In this regard, this paper presents a novel approach for in silico identification of differentially expressed miRNAs from microarray expression data sets. It integrates judiciously the theory of rough sets and merit of the so-called B.632+ bootstrap error estimate. While rough sets select relevant and significant miRNAs from expression data, the B.632+ error rate minimizes the variability and bias of the derived results. The effectiveness of the proposed approach, along with a comparison with other related approaches, is demonstrated on several miRNA microarray expression data sets, using the support vector machine.

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Prognostic significance of differentially expressed miRNAs in esophageal cancer.

Project description:Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21 and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126 and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-?(2) expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell dedifferentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e and miR-200a expression were associated with shorter overall and disease-free survival in patients with esophageal adenocarcinoma; however, miR-16-2, miR-30e and miR-200a expression were not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.

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Identification of differentially expressed genes in non-small cell lung cancer.

Project description:Lung cancer is the most common malignant tumor and the leading cause of cancer-related deaths worldwide. Because current treatments for advanced non-small cell lung cancer (NSCLC), the most prevalent lung cancer histological subtype, show limited efficacy, screening for tumor-associated biomarkers using bioinformatics reflects the hope to improve early diagnosis and prognosis assessment. In our study, a Gene Expression Omnibus dataset was analyzed to identify genes with prognostic significance in NSCLC. Upon comparison with matched normal tissues, 118 differentially expressed genes (DEGs) were identified in NSCLC, and their functions were explored through bioinformatics analyses. The most significantly upregulated DEGs were TOP2A, SLC2A1, TPX2, and ASPM, all of which were significantly associated with poor overall survival (OS). Further analysis revealed that TOP2A had prognostic significance in early-stage lung cancer patients, and its expression correlated with levels of immune cell infiltration, especially dendritic cells (DCs). Our study provides a dataset of potentially prognostic NSCLC biomarkers, and highlights TOP2A as a valuable survival biomarker to improve prediction of prognosis in NSCLC.

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