Multi-omics Analysis reveals novel therapeutic vulnerabilities in lung cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159857 | GEO | 2022/05/04
REPOSITORIES: GEO
Similar Datasets
Project description:We systematically profiled the genome-wide alternative splicing events in Lung Adenocarcinoma (LUAD) and Lung Squomous Cell Carcinoma (LUSC) against Lung Control through Human Transcriptome Array2.0. Non-invasive Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in nature which makes it difficult to predict, diagnose and prognose owing to lower 5-year survival rate and 75-85% brain or bone metastasis. Hence, we hypothesized to develop transcript-based signature to categorize Stage IIIA-NSCLC-LUAD and LUSC, as well as identify markers which could indicate towards prognosis of disease. We were able to molecularly-categorize LUAD- and LUSC-tissue more precisely through HTA array2.0.
2020-09-21 | GSE138682 | GEO
Project description:BCL11A is upregulated in lung squamous cell carcinoma (LUSC) but not in lung adenocarcinoma (LUAD). BCL11A interacts with SOX2 at protein level. ChIP-Seq experiment was performed for BCL11A and SOX2 in LUSC LK-2 control or BCL11A-KD cell line in order to identify their role in LUSC pathology.
2018-07-05 | E-MTAB-6958 | biostudies-arrayexpress
Project description:The transcription factor SOX2 required for pluripotency, is amplified in 40% of the lung squamous cell carcinoma (LUSC) cases. However, a long-term survival analysis using TCGA cohorts of LUSC patients revealed no significant differences between high versus low SOX2 expressing cases. The treatment options for irresectable LUSC are limited to chemotherapy where carboplatin or cisplatin is given in combination with gemcitabine. However, drug resistance remains a serious concern. We previously showed integrin β4 (ITGB4) and paxillin (PXN) play a critical role in platinum resistance in LUAD. Heterogenous NSCLC cells that up-regulate ITGB4 and PXN epigenetically, can switch phenotypes from cisplatin sensitive to tolerant. However, the significance of ITGB4 expression in SOX2 driven cancer stem cells (CSCs) in NSCLC remains unappreciated. In this study, we isolated CSCs from LUSC patients and characterized them. We elucidated the significance of ITGB4 and SOX2 expression in maintaining the stemness of CSCs and their response to cisplatin treatment. Finally, we showed that the proteasome inhibitor carfilzomib (CFZ) targets SOX2 dependent CSCs and this function of CFZ is independent of its proteasome inhibitory function.
2023-08-21 | GSE227899 | GEO
Project description:We conducted whole-exome sequencing (WES) and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histologic patterns including 6 LUAD, 6 LCNEC, 3 SCLC, 3 LUSC, and one poorly differentiated NSCLC-NOS.
| EGAD00001007076 | EGA
Project description:Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) is the most common subset. Although immune checkpoint inhibitors have improved outcomes in a subset of NSCLC patients, these effects are usually not durable. Thus, a more complete understanding of how immune niches within the tumor microenvironment (TME) promote NSCLC progression will allow us to build upon these advances. We previously found that infiltration of tumor inflammatory monocytes (TIMs) into lung squamous carcinoma (LUSC) tumors is associated with increased metastases and poor survival. To further understand how TIMs promote metastases, we compared RNA-seq profiles of TIMs from several LUSC metastatic models with IMs of non-tumor bearing controls. We identified Spon1, a secreted extracellular matrix glycoprotein, as upregulated in TIMs and that Spon1 expression in LUSC tumors corresponds with poor survival. Bioinformatic analyses of the Cancer Genome Atlas (TCGA) revealed that LUSC tumors with high SPON1 expression significantly enriched for collagen extracellular matrix (ECM) signatures. Unexpectedly, we observed SPON1+ TIMs mediate their effects directly through LRP8 (ApoER2) on NSCLC cells, which results in TGFβ1 activation and robust production of fibrillar collagens. Using several orthogonal approaches, we demonstrate that SPON1+ TIMs are sufficient to promote NSCLC metastases. Additionally, we find that Spon1 loss in the host, or Lrp8 loss in cancer cells, results in a significant decrease of both high-density collagen matrices and metastases. Finally, we confirm the relevance of the SPON1/LRP8/TGFβ1 axis with collagen production and survival in NSCLC patients. Taken together, our study describes how SPON1+ TIMs promotes collagen remodeling and NSCLC metastases through an LRP8-TGFβ1 signaling axis in lung cancer cells.
2024-03-05 | GSE260524 | GEO
Project description:WES sequencing of multiple regions per tumor from 8 lung cancer patients (LUSC, LCNEC and LUAD) and adjacent healthy lung tissue for each patient.
| EGAD00001008950 | EGA
Project description:The aim of this project was to identify microRNAs associated with the expression subtypes in patients diagnosed with non-small cell lung cancer. Based on mRNA expression data the samples were assign to a gene expression subtype based on 506 gene centroid classifier. The patients enrolled in this study underwent curatively intended surgical resection. Subtype-specific microRNA expression was correlated to gene set enrichment scores in order to identify associated pathways that the microRNAs may be regulating, characterizing the expression subtypes. In order to assess if the subtype-specific microRNA signal originate from the lung cancer cells or from infiltrating immune cells, we compared our subtype-specific microRNAs with the results from a study investigating human cell-specific microRNA expression. In this project the authors sequenced microRNAs from 46 primary cell types, 42 cancer cell lines and tissues (McCall MN, Kim MS, Adil M, Patil AH, Lu Y, Mitchell CJ, Leal-Rojas P, Xu J, Kumar M, Dawson VL et al: Toward the human cellular microRNAome. Genome Res 2017, 27(10):1769-1781). The results were further validated in independent NSCLC cohorts (LUAD and LUSC) from The Cancer Genome Atlas (TCGA). In this study we identified subtype specific microRNAs associated with essential processes characterizing the expression subtypes of ADs and SCCs.
2019-11-01 | E-MTAB-7954 | biostudies-arrayexpress
Project description:Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules,that are detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection.We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate pathways of lung oncogenesis.
2020-09-08 | GSE152702 | GEO
Project description:<p><a href="https://cptac-data-portal.georgetown.edu/study-summary/S056" target="_blank">Proteogenomics of Lung Adenocarcinoma, Gillette et al., 2020 publication is here</a><br><br>Lung cancer is a leading cause of cancer death in the United States and in 2019 it is estimated that there will be over 228,000 new cases (<a href="https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html" target="_blank">American Cancer Society</a>). There are two main types, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). A majority of patients (85%) have NSCLC, with a significant portion of those individuals having a histological subtype lung adenocarcinoma (LUAD) <a href="https://www.ncbi.nlm.nih.gov/pubmed/29364287" target="_blank">Herbst et al., 2018 Nature</a>. To advance the proteogenomic understanding of LUAD, the CPTAC program has investigated 111 tumors, (with 102 tumors paired with normal adjacent tissue samples) and subjected these samples to global proteome and phosphoproteome analysis. An optimized workflow for mass spectrometry of tissues using isobaric tags (TMT (tandem mass tags)-10) was used (<a href="https://www.ncbi.nlm.nih.gov/pubmed/29988108" target="_blank">Mertins et al., Nature Protocols 2018</a>). Proteome and phosphoproteome data from the LUAD discovery cohort is available below along with peptide spectrum matches (PSMs) and protein summary reports from the CPTAC common data analysis pipeline (CDAP).</p><p><em>Clinical Data</em> for LUAD tumors are provided below. Updates will be available as the LUAD cohort characterization proceeds.<br><em>Genomic Data</em> for LUAD tumors is available from the NCI Genomic Data Commons (GDC), <a href="https://portal.gdc.cancer.gov/projects/CPTAC-3" target="_blank">here</a><br><em>Imaging Data</em> for LUAD tumors is available from NCI, The Cancer Imaging Archive (TCIA), <a href="https://wiki.cancerimagingarchive.net/display/Public/CPTAC-LUAD" target="_blank">here</a><br>This release includes over 4500 files and 914 GB of data.</p>
<ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S046">https://cptac-data-portal.georgetown.edu/study-summary/S046</a> on 01/29/21</li></ul>
2021-02-01 | MSV000086793 | MassIVE
Project description:Lung cancer is the leading cause of cancer-related mortality. The two main lung cancer types are small cell lung cancer (SCLC) and non-SCLC (NSCLC), where NSCLC comprises about 80-85% of all lung cancer. Despite the introduction of improved treatments, the overall survival rate of lung cancer patients remains low. Further elucidation of the regulatory network perturbations between cancer-related genes and proteins is one promising route to alter this mortality trend. The deregulation of the DNA replication, cell cycle, proliferation and migration are the common factors that are involved in cancer development and progression, and therefore logical targets for analysis. Minichromosome maintenance 2(MCM2) is a DNA replication licensing factor, which belongs to the heterohexameric MCM2-7 complex. MCM2 has been proposed as an excellent proliferation marker in many types of cancer. Our study will establish a global functional distribution of identified proteins in silenced-MCM2 in H1299 NSCLC by the means of iTRAQ. Understanding the molecular basis of MCM2 in lung cancer cells enables us to discover alternative target for lung cancer therapy.
2018-10-26 | PXD003743 | Pride