Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: phs000299.v1.p1
PROVIDER: PRJNA125281 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Data-independent acquisition (DIA) mass spectrometry (MS) data acquisition and targeted data extraction has become a promising strategy with enhanced identification coverage and consistent quantitation across multiple samples. However, coverage at the genome-depth still awaits to be improved. Here, we established a high quality proteome reference library from five lung cancer cell lines varying in epidermal growth factor (EGFR) mutation status and twenty two pooled patient-derived lung tumor tissues samples. By using high pH reverse phase (HpRP) fractionation, we were able to achieve 12,344 protein groups (223,091 unique peptide sequences, 344,430 precursors) from 191 data dependent acquisition (DDA) raw files acquired over similar chromatographic and Orbitrap Fusion Lumos MS platform, at 1% PSM and protein level false discovery rate (FDR). Application to tissue and cell line derived peptides also showed deep profiling of library based DIA. The established spectra library provides a useful resource for deep quantitative sensitive proteome profiling of clinical samples.
2021-03-05 | PXD019916 | JPOST Repository
Project description:Background
Cancer is one of the leading causes for the morbidity and mortality worldwide. Although substantial studies have been conducted theoretically and experimentally in recent years, it is still a challenge to explore the mechanisms of cancer initiation and progression. The investigation for these problems is very important for the diagnosis of cancer diseases and development of treatment schemes.
Results
To accurately describe the process of cancer initiation, we propose a new concept of gene initial mutation rate based on our recently designed mathematical model using the non-constant mutation rate. Unlike the widely-used average gene mutation rate that depends on the number of mutations, the gene initial mutation rate can be used to describe the initiation process of a single patient. In addition, we propose the instantaneous tumour doubling time that is a continuous function of time based on the non-constant mutation rate. Our proposed concepts are supported by the clinic data of seven patients with advanced pancreatic cancer. The regression results suggest that, compared with the average mutation rate, the estimated initial mutation rate has a larger value of correlation coefficient with the patient survival time. We also provide the estimated tumour size of these seven patients over time.
Conclusions
The proposed concepts can be used to describe the cancer initiation and progression for different patients more accurately. Since a quantitative understanding of cancer progression is important for clinical treatment, our proposed model and calculated results may provide insights into the development of treatment schemes and also have other clinic implications.
2020-02-28 | BIOMD0000000915 | BioModels
Project description:Lung cancer is the leading cause of cancer death both in men and women. Tumor heterogeneity is an impediment to targeted treatment of all cancers, including lung cancer. Here, we sought to characterize changes in tumor proteome and phosphoproteome by longitudinal, prospective collection of tumor tissue of an exceptional responder lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for more than seven years with HER2-directed therapy in combination with chemotherapy. We employed “Super-SILAC” and TMT labeling strategies to quantify the proteome and phosphoproteome of a lung metastatic site and ten different metastatic progressive lymph nodes collected across a span of seven years, including five lymph nodes procured at autopsy. We identified specific signaling networks enriched in lung compared to the lymph node metastatic sites. We correlated the changes in protein abundance with changes in copy number alteration (CNA) and transcript expression. To further interrogate the mass spectrometry data, patient-specific database was built incorporating all the somatic variants identified by whole genome sequencing (WGS) of genomic DNA from the lung, one lymph node metastatic site and blood. An extensive validation pipeline was built for confirmation of variant peptides. We validated 360 spectra corresponding to 55 germline and 6 somatic variant peptides. Targeted MRM assays demonstrated expression of two novel variant somatic peptides, CDK12 G879V and FASN-R1439Q, with expression in lung and lymph node metastatic sites, respectively. CDK12 G879V mutation likely results in a nonfunctional kinase and knockdown of CDK12 in lung adenocarcinoma cells increased chemotherapy sensitivity, explaining the complete resolution of the lung metastatic sites in this patient.
2019-01-07 | PXD010779 | Pride
Project description:Genome-wide DNA methylation study in lung cancer and paired normal lung with well-documented asbestos exposure
2017-07-24 | GSE94785 | GEO
Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162945 | GEO
Project description:Background and purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens.
2020-12-10 | GSE162944 | GEO
Project description:We leveraged massively parallel sequencing approach to comprehensively characterize the spectrum of somatic mutations and genomic rearrangements in two intestinal-type gastric adenocarcinomas from patients with and without active Helicobacter pylori infections. The tumours exhibited distinct patterns of genomic changes with more than 16,000 somatic substitutions on average, focal amplifications and rearrangements in the non-active infected tumour and a 7-fold enrichment of micro-deletions in the infected tumour. Paired-end sequences from large insert libraries revealed the structure and origins of large amplicons, including one involving the oncogene KRAS. The mutational frequencies of the tumours revealed patterns of H. pylori infection and mutagenesis and a unique exome signature, providing insights into mechanisms that define the mutational landscape of gastric cancer. For the tumour with active infection, we also reconstructed the genome of the pathogenic H. pylori strain from the raw sequence reads, demonstrating the power of whole-genome shotgun sequencing for simultaneously characterizing the tumour and its associated carcinogen genome.
2012-12-05 | GSE30833 | GEO
Project description:Protein glycosylation plays a fundamental role in a multitude of biological processes, and the associated aberrant expression of glycoproteins in cancer has made them attractive targets as biomarkers and therapeutic targets. In this study, we examined differentially expressed glycoproteins in cell lines derived from three different states of lung tumorigenesis: an immortalized bronchial epithelial cell (HBE) line, a non-small cell lung cancer (NSCLC) cell line harboring an activation KRAS mutation and a NSCLC cell line harboring an EGFR activation deletion. Mutations in KRAS and EGFR are two common, distinct, non-overlapping genomic alterations in NSCLC. Using a Triple SILAC proteomic quantification strategy paired with hydrazide chemistry N-linked glycopeptide enrichment, we identified 118 quantifiable glycopeptides in the 3 cell lines derived from 82 glycoproteins. Proteomic profiling revealed that 27 (24%) of the glycopeptides overexpressed in both of the NSCLC cell lines with 6 of the glycopeptides overexpressed only in the EGFR mutant cells and 19 of the glycopeptides overexpressed only in the KRAS mutant cells.
2015-12-10 | PXD001999 | Pride
Project description:During pancreatic cancer progression, heterogeneous subclonal populations evolve in the primary tumor that possess differing capacities to metastasize and cause patient death. However, the genetics of metastasis reflects that of the primary tumor, and PDAC driver mutations arise early. This raises the possibility than an epigenetic process could be operative late. Using an exceptional resource of paired patient samples, we found that different metastatic subclones from the same patient possessed remarkably divergent malignant properties and global epigenetic programs. Global reprogramming was targeted to thousands of large chromatin domains across the genome that collectively specified malignant divergence. This was maintained by a metabolic shift within the pentose phosphate pathway, independent of KRAS driver mutations. Analysis of paired primary and metastatic tumors from multiple patients uncovered substantial epigenetic heterogeneity in primary tumors, which resolved into a terminally reprogrammed state in metastatic lesions. This supports a model whereby driver mutations accumulate early to initiate pancreatic tumorigenesis, followed by a period of subclonal evolution that generates sufficient intra-tumor heterogeneity for selection of epigenetic programs that may increase fitness during malignant progression and metastatic spread. To map the epigenomic landscape of pancreatic cancer progression as it evolves within patients. Chip-Seq (K27Me3, K36Me3, K9Me2/3, K4Me3 and K27Ac) of 2 patients (A13 and A38) and HPDE cell line. Patient A38 included local peritoneal metastasis and 2 distant metastsis (liver and lung mets), and 6AN treated and DMSO samples for lung matastasis. Patient A13 included 2 primary tumors and 1 distant lung metastasis. Each sample has been done with replicates.
2016-10-24 | E-GEOD-63125 | biostudies-arrayexpress