Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteome Analysis of Non-Small Cell Lung Cancer Cell Line Secretomes and Patient Sputum Reveals Biofluid Biomarker Candidates for Cisplatin Response Prediction

ABSTRACT: We profiled the secretomes of six NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2618 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins, in line with enhanced levels of non-conventional secretion in cisplatin insensitive cell lines. Stringent statistical analysis and quantitative filtering yielded 41 top biomarker candidates, many of which could also be detected in NSCLC patient sputum using label-free GeLC-MS/MS-based proteomics. A published gene expression dataset was used to determine which of our top secretome cisplatin response prediction candidates might have predictive value in terms of overall survival in patients that received platinum-based treatment. This analysis yielded two cisplatin sensitivity (UGGT1 and MATN2) and one cisplatin resistance (MAP4) candidates that may serve as potential biomarkers for cisplatin response prediction in NSCLC patients in the future.

INSTRUMENT(S): LTQ FT, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD005830 | Pride | 2022-02-28

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	100923_03.RAW	Raw
	100923_05.RAW	Raw
	100923_07.RAW	Raw
	100923_09.RAW	Raw
	100923_101.RAW	Raw

Items per page:

1 - 5 of 148

Similar Datasets

Proteome Analysis of Non-Small Cell Lung Cancer Cell Line Secretomes and Patient Sputum Reveals Biofluid Biomarker Candidates for Cisplatin Response Prediction

Project description:We profiled the secretomes of 6 NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2618 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins. Stringent statistical analysis and quantitative filtering yielded 58 biomarker candidates, 34 of which could be detected in clinical biofluids of lung cancer patients such as sputum using label-free LC-MS/MS-based proteomics. To assess performance of these biofluid biomarker candidates, we correlated protein expression with patient survival using a publically available clinical gene expression data set (GSE14814). We thus identified 3 top candidates with potential predictive value in determining cisplatin response (UGGT1, COL6A1 and MAP4) for future development as non-invasive biomarkers to guide treatment decisions.

2019-02-15 | PXD011315 | Pride

Single cell RNA-seq atlas of human NSCLC lesions and non-involved tissue

Project description:We performed single cell RNA sequencing (scRNA-seq) of NSCLC tumours and matched, adjacent, non-involved lung tissue from 24 patients. The data set is composed of approximately 900,000 cells from two different populations: CD235- (haematopoietic and non-haematopoietic cells depleted of erythrocytes), and CD45+ (all haematopoietic cells).

2024-04-29 | E-MTAB-13526 | biostudies-arrayexpress

CRTAC1 Enhances the Chemosensitivity of Non-Small Cell Lung Cancer to Cisplatin by Eliciting RyR-mediated Calcium Release and Inhibiting Akt1 Expression

Project description:Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in the patients of non-small cell lung cancer (NSCLC). Here, our results obtained from analyses of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca2+ levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation, and in turn enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca2+-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.

2023-08-29 | PXD041782 | Pride

MigExpress discovers essential cell migration control genes in non-small cell lung cancer

Project description:Cell migration is an essential process in health and disease - especially in cancer metastasis. The difficulty to assess migration in high throughput presents a methodological hurdle - hence, only very few screens revealed factors controlling this important process. Here, we introduce MigExpress as a platform for the "identification of Migration control genes by differential Expression". MigExpress exploits the combination of in-depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration-associated genes by their differential expression in slowly versus fast migrating cells. We applied MigExpress to non-small cell lung cancer (NSCLC), the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6 and BICC1 as migration control factors in NSCLC cells, which also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage.

2021-04-20 | PXD022146 | Pride

Tumor heterogeneity underlies differential cisplatin sensitivity in mouse models of small cell lung cancer

Project description:SCLC is the most aggressive subtype of lung cancer characterized by a remarkable response to chemotherapy followed by development of resistance. Mechanisms of initial sensitivity and of subsequent resistance are not understood. Here we highlight a broad tumor heterogeneity in mouse models of SCLC, which includes a CDH1 high primary cisplatin-resistant peripheral neuroendocrine lesion with unique metabolic and structural profile. Cisplatin treatment preferentially eliminates CDH1 negative secondary tumor leaving behind CDH1 high primary lesions, thus revealing a striking differential response. We profile global protein and messenger RNA levels in vehicle and cisplatin treated lung tumor populations and find a marked reduction in proliferation and a pronounced metabolic shift following cisplatin-treatment. Our proteo-transcriptomic analysis gives insight into gene expression alterations that characterize cisplatin resistance and uncovers potential novel targets to overcome resistance of distinct populations. SCLC tumors in the mouse show heterogeneity which appears, as might be the case in humans, to be one of the underlying mechanisms of differential sensitivity to cisplatin.

2019-11-12 | PXD010680 | Pride

Identification of proteome changes in apoptotic NSCLC cells

Project description:Here, we used an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens. Only the fragmented proteins elicited effective multi-specific T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased significantly upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression.

2020-05-27 | PXD016997 | Pride

Integration of metabolomics and transcriptomics to reveal metabolic characteristics and key targets associated with cisplatin resistance in non-small cell lung cancer

Project description:Continuous exposure to cisplatin can induce drug resistance to limit efficacy, however, the underlying mechanisms correlated to cisplatin resistance are still unclear. Drug-sensitive A549 cells and cisplatin-resistant A549/DDP cells were used to explore the potential metabolic pathways and key targets associated with cisplatin resistance by integrating untargeted metabolomics with transcriptomics. The results of comprehensive analyses showed that 19 metabolites were significantly changed in A549/DDP vs A549 cells, and some pathways had a close relationship with cisplatin resistance, such as the biosynthesis of aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism. Moreover, transcriptomics analysis showed glutathione metabolism was also obviously affected in A549/DDP, which indicated that glutathione metabolism played an import role in the process of drug resistance. Meanwhile, transcriptomics analysis suggested the four enzymes related to glutathione metabolism - CD13, GPX4, RRM2B, and OPLAH - as potential targets of cisplatin resistance in NSCLC. Further studies identified the over-expressions of these four enzymes in A549/DDP. The elucidation of mechanism and discovery of new potential targets may help us have a better understanding of cisplatin resistance.

2019-08-12 | PXD013265 | Pride

Combined expression of plasma CA19-9 and thrombospondin-2 for accurate diagnosis of pancreatic cancer and distal cholangiocarcinoma– A proteome approach

Project description:Minimally- invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (CCA) are warranted to enhance early and accurate diagnosis. This study identified tumor tissue secreted proteins, the “secretome”, which was analysed for differential candidate diagnostic plasma proteins. Secretome of tumor and normal tissue was collected directly after resection of the primary tumor from 4 patients with PDAC and distal CCA. The tissue secretome was investigated by label-free LC-MSMS, and database searching identified a total of 5179 proteins. 696 proteins were differentially enriched in tumor secretome compared to normal tissue. Thrombospondin-2 (THBS2) emerged as most promising candidate diagnostic biomarker. Subsequent analysis of THBS2 in plasma samples of patients with PDAC and distal CCA by ELISA showed significantly higher abundance compared to healthy individuals (p<0.001) and resulted in an AUC of 0.844.

2020-05-26 | PXD012480 | Pride

Time-course gene expression profiles of gefitinib-sensitive or -resistant lung adenocarcinoma cells stimulated with EGF, in the presence or absence of gefitinib, EGF receptor tyrosine kinase-specific inhibitor

Project description:Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), induces substantial clinical responses for non-small cell lung cancer (NSCLC) cells harboring EGFR activating mutations, but most of them invariably develop resistance. By generating a gefitinib resistance (PC9GR) from a human NSCLC-derived drug sensitive cell line (PC9), we studied differences of transcription dynamics between them by the aid of a computational decoupling of hidden regulatory signals from time course gene expression profiles. Given a collection of transcription factors (TFs) and their regulatory targets, the method captured temporally-synchronized shifts in evolving expression of target genes sharing each TF regulatory unit, and drew underlying regulatory signals. The analysis identified sterol regulatory element binding protein 1 (SREBP-1) as a key regulatory agent that facilitates the maintenance of drug tolerance, involving transcription controls of a G1-specific cyclin dependent kinase inhibitor whose expression was specifically elevated in PC9, but in turn, reduced in PC9GR Gefitinib-resistance cell line (PC9GR) was established derived from lung adenocarcinoma cell line PC9. PC9 cells and PC9GR cells were treated with the four different conditions, control (No treatment), EGF-treatment, gefitinib-treatment, and both gefitinib and EGF-treatment. In each condition, the gene expression was measured at 26 time points during 24 hrs.

2014-01-01 | E-GEOD-34228 | biostudies-arrayexpress

Gene expression data from human NSCLC U1810 residual clones 9 days after a one-hour pulse treatment with cisplatin

Project description:Background: The platinum compounds cisplatin and carboplatin are the mainstay of chemotherapy for lung cancer; however, treatment failure remains a critical issue since about 60% of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. Methods: We analyzed global gene expression profiles in NSCLC clones surviving a pulse treatment with cisplatin by microarray and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Results: Cisplatin-surviving NSCLC clones were demonstrated to have heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (DKK1), DNA repair machinery (XRCC2) and cell-cell/ cell-matrix interaction (FMN1 and LGALS9) were among the top deregulated genes by microarray and were subsequently validated by q-RT-PCR. We focused on DKK1, which was previously reported to be overexpressed in NSCLC. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones. Knockdown of DKK1 by siRNA sensitized untreated NSCLC cells to cisplatin, illustrating a putative role of DKK1 in intrinsic platinum resistance. Conclusions: Gene expression analysis identified DKK1 as a putative cisplatin resistance marker and a potential novel therapeutic target to overcome platinum resistance in NSCLC. U1810 cells were sparsely seeded for clonogenic survival assay in three separate experiments (replicate 1-3), left untreated or treated with cisplatin for 1 h and then kept for 9 days to assay long-term effects of a single pulse treatment.

2014-04-04 | E-GEOD-48244 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data