Molecular determinants of tumor behavior in early lung adenocarcinoma
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ABSTRACT:
PROVIDER: PRJNA533155 | ENA |
REPOSITORIES: ENA
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Project description:Molecular determinants of tumor behavior in early lung adenocarcinoma
| PRJNA533154 | ENA
Project description:Clinical FFPE tissue proteomic analyses were performed for early lung adenocarcinomas including adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPA).
2020-01-30 | PXD017334 | JPOST Repository
Project description:To characterize the etiology of lung adenocarcinoma (LUAD) in the United States, we performed deep proteogenomic profiling of 87 tumors integrating whole genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry and reverse phase protein arrays. Somatic genome signature analysis revealed three subtypes including a structurally altered subtype enriched with former smokers, genomic inversions and deletions and TP53 alteration, a transition-high subtype enriched with never-smokers, and a transversion-high enriched with current smokers. We discovered that within-tumor correlations of RNA expression and protein expression were associated with tumor purity, grade, immune cell heterogeneity, and expression subtype. We detected and independently validated RNA and protein expression signatures predicting patient survival. A greater number of proteins than RNA transcripts had association with patient survival. Integrative analysis characterized three expression subtypes with divergent mutations, proteomic regulatory networks and therapeutic vulnerabilities. This proteogenomic characterization provides a new foundation for molecularly-informed medicine in LUAD.
2022-11-16 | PXD036025 | Pride
Project description:Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants.Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs.Methods: DNA was extracted from 21 ADCs in situ (AISs), 27 minimally invasive ADCs (MIAs), and 54 fully invasive ADCs. This DNA was subjected to deep next-generation sequencing and tested against a custom panel of 347 cancer genes.Measurements and Main Results: Sequencing data was analyzed for associations among tumor mutation burden, frequency of mutations or copy number alterations, mutation signatures, intratumor heterogeneity, pathway alterations, histology, and overall survival. We found that deleterious mutation burden was significantly greater in invasive ADC, whereas more copy number loss was observed in AIS and MIA. Intratumor heterogeneity establishes early, as in AIS. Twenty-one significantly mutated genes were shared among the groups. Mutation signature profiling did not vary significantly, although the APOBEC signature was associated with ADC and poor survival. Subclonal KRAS mutations and a gene signature consisting of PIK3CG, ATM, EPPK1, EP300, or KMT2C mutations were also associated with poor survival. Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers.Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.
| S-EPMC7068818 | biostudies-literature
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.
2019-06-26 | GSE101684 | GEO
Project description:The World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC), adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns Pure invasive adenocarcinomas are often devoid of bronchioloalveolar morphology. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in non-mucinous BAC is significantly lower than that of pure invasive tumors and in tumors with greater than 0.6 cm of fibrosis or linear invasion (J Thorac Oncol 6:244-285) To identify human tumor cell signatures associated with lung adenocarcinoma subtype and invasion, we performed microarray gene expression profiling of microdissected tumor cells noninvasive AC and AC-Mixed invasive tumors. 17 cases of noninvasive AC tumors and 23 cases of AC-mixed subtype invasive lung adenocarcinomas resected from 2002 to 2006 were examined (Columbia Lung Adenocarcinoma dataset)
2011-09-14 | E-GEOD-27716 | biostudies-arrayexpress
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.
2012-03-21 | E-GEOD-32863 | biostudies-arrayexpress
Project description:To investigate the mechanism associated with cis-platin intrinsic resistance, we established a model of early drug-tolerant persister cells by exposing lung adenocarcinoma cell lines to the drug for 24 h. Then, we analyzed the transcriptome using RNA-seq from 4 different lung adenocarcinoma cell lines.
2023-11-03 | GSE213102 | GEO
Project description:The World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC), adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns Pure invasive adenocarcinomas are often devoid of bronchioloalveolar morphology. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in non-mucinous BAC is significantly lower than that of pure invasive tumors and in tumors with greater than 0.6 cm of fibrosis or linear invasion (J Thorac Oncol 6:244-285) To identify human tumor cell signatures associated with lung adenocarcinoma subtype and invasion, we performed microarray gene expression profiling of microdissected tumor cells noninvasive AC and AC-Mixed invasive tumors.
2011-09-15 | GSE27716 | GEO
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.
2022-02-01 | GSE166720 | GEO