Project description:To determine the circRNA expression profile in early stage lung adenocarcinoma and matched non-tumor tissues, we used circRNA microArray analysis form Arraystar to examine the expression of circRNAs Lung adenocarcinoma, a form of NSCLC with high lethality at advanced stage, is becoming more popular in women, non- or never-smokers, and even young adult. However, there are no effective early diagnosis methods at present for patients to cure timely. Circular RNAs (circRNAs) as a special novel, stable, and conserved non-coding RNA in mammalian cells have been reported to be widely involved in the processes of cancer disease. Yet, it is still a puzzle which specific circRNAs are involved in the development of early stage lung adenocarcinoma. Here, tumour samples and paired adjacent normal tissues from 4 patients with early stage lung adenocarcinoma were selected for investigating the expression profile of circRNAs by using the high-throughput circRNA microarray. Bioinformatic analyses were conducted to screen those differentially expressed circRNAs. This work illustrates that clusters of circRNAs are aberrantly expressed in early stage lung adenocarcinoma, which might be able to provide potential targets for the early diagnosis of this disease and new genetic insights into lung cancer.
Project description:To determine the lncRNA expression profile in Lung adenocarcinoma (LAD) with or without lymph node metastasis and matched non-tumor tissues, we uesed lncRNA microArray analysis form Arraystar to examine the expression of lncRNAs in LAD with or without lymph node metastasis and matched non-tumor tissues.
Project description:Genome wide DNA methylation profiling of Stage I Lung Adenocarcinoma and non-tumor adjacent tissues. The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included tumor and adjacent non-tumor tissues excised from a cohort of 35 patients with Stage I Lung Adenocarcinoma. Candidate prognostic biomarkers were validated by pyrosequencing in independent cohorts.
Project description:This SuperSeries is composed of the following subset Series: GSE32861: Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression GSE32863: Gene expression analysis of lung adenocarcinoma and matched adjacent non-tumor lung tissue GSE32866: Genome-scale DNA methylation profiling of lung adenocarcinoma: validation using Ontario Tumor Bank samples Refer to individual Series
Project description:This study was undertaken to identify novel tumour suppressor genes in lung adenocarcinoma. EYA4, located at 6q23.2 was identified as a frequently lost and hypermethylated gene in the analyzed samples. EYA4 is underexpressed in addition to being deleted and hypermethylated. Control of EYA4 expression by DNA methylation was assessed using 5'-azacytidine. The role of EYA4 in apoptosis was assessed using a stable knock down of the gene which was assessed for apoptotis using FACS and qPCR. Methylation profiling: 30 adenocarcinoma samples and 30 patient-matched non-malignant lung samples are included. Non-malignant samples were used as references to identify hypermethylated probes. For each normal/tumor pair, the sample numbers are paired but offset by one with the tumor being the lower of the two numbers. For example, 85040001 is the adenocarcinoma tumor profile that pairs with non-malignant 85040002. Genome variation (aCGH) profiling: 30 adenocarcinoma gene dosage profiles are included. Values presented are log2 ratios of Cy3(sample)/Cy5(diploid reference)
Project description:microRNA expression profiling of Stage I Lung Adenocarcinoma and non-tumor adjacent tissues. The Nanostring nCounter Human miRNA Expression Assay Kit version 1.6 (Nanostring, Seattle, WA) was used to obtain microRNA profiles of tumor and adjacent non-tumor tissues excised from Stage I Lung Adenocarcinoma patients.
Project description:Gene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes. Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation.
Project description:Gene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes. Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation. 58 lung adenocarcinoma and 58 adjacent non-tumor lung fresh frozen tissues were macrodissected, and total RNA was isolated to be analyzed using the Illumina HumanWG-6 v3.0 expression beadchip.
Project description:Lung adenocarcinoma is the most common histological subtype of lung cancer. Although early-stage LUAD (esLUAD) patients have much better prognosis than patients with advanced disease, among early stage patients treated primarily with surgery, some of early stage patients will develop metastasis with overall 5 year survival for stage 1 and 2 non-small cell lung cancer of 70% and 35%, respectively. Within lung adenocarcinoma, histology is heterogenous and associated with tumor invasion and clinical outcomes. Invasiveness is one of cancer hallmarks and is directly related with metastatic potential and clinical outcomes of the tumor. In this study, we characterize invasiveness mechanisms in esLUAD by analyzing gene expression of a novel cohort of 53 histologically heterogenous esLUAD samples.