Project description:Lung adenocarcinoma subtypes definable by lung development-related miRNA expression profiles in association with clinicopathologic features [miRNA analysis - miRNA Microarray, pre-commercial version 6.0]
Project description:Lung adenocarcinoma subtypes definable by lung development-related miRNA expression profiles in association with clinicopathologic features [pre-miRNA analysis - Whole Human Genome 4 x 44K Microarray]
Project description:Lung adenocarcinoma subtypes definable by lung development-related miRNA expression profiles in association with clinicopathologic features [mRNA analysis - Whole Human Genome 4 x 44K Microarray]
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development. Microarray analysis was conducted to examine miRNA expression profiles using a Human miRNA Microarray, pre-commercial version 6.0 (Agilent) with 470 miRNA probes, according to the manufacturer’s instructions
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development. Microarray analysis using a Whole Human Genome 4 x 44K Microarray G4112F (Agilent) was conducted.
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development. Microarray analysis using a Whole Human Genome 4 x 44K Microarray G4112F (Agilent) was conducted to examine changes in expression of 400 genes in SiGN network by transfection of Pre-miR-30d, Pre-miR-195 or Pre-miR-NC#2 (Ambion) in SK-LC-7 cells, which were then harvested at 72 hours after transfection.
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development.
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development.
Project description:Accumulation of genetic and epigenetic changes alters regulation of a web of interconnected genes including miRNAs, which confer hallmark capabilities and characteristic cancer features. In this study, the miRNA and mRNA expression profiles of 126 non-small cell lung cancer specimens were analyzed, with special attention given to the diversity of lung adenocarcinomas. Of those, 76 adenocarcinomas were classified into two major subtypes, developing lung-like and adult lung-like, based on their distinctive miRNA expression profiles resembling those of either developing or adult lungs, respectively. A systems biology-based approach using a Bayesian network and nonparametric regression was employed to estimate the gene regulatory circuitry functioning in patient tumors in order to identify subnetworks enriched for genes with differential expression between the two major subtypes. miR-30d and miR-195, identified as hub genes in such subnetworks, had lower levels of expression in the developing lung-like subtype, while introduction of miR-30d or miR-195 into the lung cancer cell lines evoked shifts of mRNA expression profiles towards the adult lung-like subtype. Conversely, the influence of miR-30d and miR-195 was significantly different between the developing lung- and adult lung-like subtypes in our analysis of the patient dataset. In addition, RRM2, a child gene of the miR-30d-centered subnetwork, was found to be a direct target of miR-30d. Together, our findings reveal the existence of two miRNA expression profile-defined lung adenocarcinoma subtypes with distinctive clinicopathologic features and also suggest the usefulness of a systems biology-based approach to gain insight into the altered regulatory circuitry involved in cancer development.
Project description:Squamous cell lung cancer (SCC) and adenocarcinoma are the most common subtypes of the lung tumours. The search for cancer-directed treatments has increased the need for understanding molecular features of either histological subtype. The aim of this study was to identify transcriptional regulation differences due to miRNA expression profiles between SCC and adenocarcinoma. For this propose, a total of 44 patients were evaluated to assess the correlation between the miRNA and messenger RNA (mRNA) expression levels. Total RNA were isolated, amplified, labeled and hybridized on Agilent human whole genome V2 22 K microarray chip. qRT-PCR was conducted to validate our microarray data. MicroRNA expression was detected and quantified using the TaqMan Low Density Arrays. Predicted miRNA-mRNA interactions were taken from miRanda, miRWalk and TargetScan. After processing data, changes in 56 mRNAs as well as in 9 miRNAs were detected between SCC and adenocarcinoma. Nearly 20% of overall deregulated genes were targeted by at least one of the 9 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a, miR-483-5p, miR-494, miR-601 and miR-708) differentially expressed between SCC and adenocarcinoma. Genes predicted (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) to be targeted by several miRNAs were individually validated by qRT-PCR. We found genes involved in tight junctions and other involved in resistance to anticancer agents. These genes were reliable biomarkers, with high sensitivity and specificity, to detect differences between the two most common histological subtypes of lung cancer. In conclusion, our data demonstrate that the transcriptional regulation differences through miRNA expression play an important role in key hallmarks of non-small cell lung cancer. Identification of new molecular markers in lung carcinoma 44 tumour samples following surgical resection for clinical early stage NSCLC (SCC and adenocarcinoma) This series represents the mRNA profiling only (not miRNA). The related miRNA data are in Series GSE43000.