Dataset Information

Platelet proteome is affected by cancer presence and therapy

ABSTRACT: Platelets play an important role in primary hemostasis, inflammation , (tumor) angiogenesis and cancer metastasis. Platelets are produced by megakaryocytes in the bone marrow and contain numerous bioactive proteins (e.g. growth factors, chemokine’s and proteases). These proteins inside platelets are either synthesized by the parental megakaryocytes or absorbed from the (micro)circulation. Therefore, it was postulated that changes in platelet protein content might indicate the presence or recurrence of a malignant tumor. We followed up the notion that both cancer and cancer therapy affect the platelet proteome. The aim of the current study was 1) to identify a pan-cancer proteome signature that could be used to discriminate patients with cancer from healthy individuals, and 2) to investigate the effect of cancer therapy on the platelet proteome. In this study, we included patients with cancer and healthy controls. Using global protein profiling by mass spectrometry-based proteomics we determined that the platelet proteome is affected by both cancer presence and antitumor therapy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Platelet

DISEASE(S): Rectum Cancer,Anus Cancer,Colon Cancer,Tongue Squamous Cell Carcinoma,Stomach Carcinoma

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD010380 | Pride | 2021-09-08

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MaxQuantzippedfolder.zip	Other
	QE2_140821_OPL1020_MW_Patient_platelet_LYSATES_PA1.raw	Raw
	QE2_140821_OPL1020_MW_Patient_platelet_LYSATES_PA2.raw	Raw
	QE2_140821_OPL1020_MW_Patient_platelet_LYSATES_PA3.raw	Raw
	QE2_140821_OPL1020_MW_Patient_platelet_LYSATES_PA4.raw	Raw

Items per page:

1 - 5 of 124

Publications

Effects of Cancer Presence and Therapy on the Platelet Proteome.

Walraven Maudy M Sabrkhany Siamack S Knol Jaco C JC Dekker Henk H de Reus Inge I Piersma Sander R SR Pham Thang V TV Griffioen Arjan W AW Broxterman Henk J HJ Oude Egbrink Mirjam M Verheul Henk M W HMW Jimenez Connie R CR

International journal of molecular sciences 20210730 15

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the sta ...[more]

PMID: 34361002

Similar Datasets

Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Experiment Overall Design: There are 18 sickle cell samples and 12 control samples from healthy African American volunteers.

Project description:Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. The aim of this study was to investigate whether differences in miRNA expression levels in platelets can be found (i) between patients with premature CAD and healthy controls and (ii) within healthy controls after and before aspirin and statin administration. In this case-control study we measured expression levels of platelet miRNAs using microarrays from 40 male patients with premature CAD and 40 age- and sex-matched healthy controls. Premature CAD was defined as a cardiac event before the age of 51 years. The patients were selected from the outpatient clinic of the Academic Medical Center (AMC) of Amsterdam, which is specialised in premature CAD. The control cohort was composed of 40 healthy Caucasian male volunteers, who were recruited by advertisement and who were matched with the cases for age and smoking habits. Individuals of this control cohort did not have a history of CVD, nor did they have a positive family history of CVD and they were not allowed to use any medication. Patients and controls were excluded when they suffered from diabetes. Most CAD patients use aspirin and statins as secondary prevention. The influence of these drugs on miRNA profiles is unknown. To assess the possible influence of medication on miRNA expression and to control for medication as confounding factor, we asked 27 volunteers in our control cohort to also use these drugs. We administered simvastatin 40 mg, once daily, for 6 weeks and during the last two weeks we added 100mg of acetyl salicylic acid, once daily. Blood samples including isolated platelets were collected at baseline in the absence of aspirin and statins and after six weeks of medication use. We also assessed platelet function using the Multiplate® Analyzer (Roche) in the absence of aspirin and statin use. In short, 300 µl whole blood was diluted with 300 µl 0.9% saline and stirred for 3 minutes at 37 ºC. Adenosine diphosphate (ADP) was added in a final concentration of 2.5 ?mol/L to initiate platelet aggregation. Aggregation was measured for 6 minutes and was reported in arbitrary aggregation units plotted against time. Also, the area under the aggregation curve (AUC) was measured. All samples were measured in the absence and presence of 200 ?mol/L indomethacin (20 min incubation with blood) to mimic the effect of aspirin use. We calculated the percentage reduction in AUC after incubation with indomethacin as an in vitro measure of the effect of aspirin use on whole blood platelet aggregation.