Emerging applications of tumour-educated platelets in the detection and prognostication of ovarian cancer.
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ABSTRACT:
SUBMITTER: Zhu J
PROVIDER: S-EPMC10392028 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Emerging applications of tumour-educated platelets in the detection and prognostication of ovarian cancer.
Zhu Jiewei J Giannakeas Vasily V Narod Steven A SA Akbari Mohammad R MR
Protein & cell 20230801 8
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Project description:BackgroundStudies have shown that blood platelets contain tumour-specific mRNA profiles tumour-educated platelets (TEPs). Here, we aim to train a TEP-based breast cancer detection classifier.MethodsPlatelet mRNA was sequenced from 266 women with stage I-IV breast cancer and 212 female controls from 6 hospitals. A particle swarm optimised support vector machine (PSO-SVM) and an elastic net-based classifier (EN) were trained on 71% of the study population. Classifier performance was evaluated in the remainder (29%) of the population, followed by validation in an independent set (37 cases and 36 controls). Potential confounding was assessed in post hoc analyses.ResultsBoth classifiers reached an area under the curve (AUC) of 0.85 upon internal validation. Reproducibility in the independent validation set was poor with an AUC of 0.55 and 0.54 for the PSO-SVM and EN classifier, respectively. Post hoc analyses indicated that 19% of the variance in gene expression was associated with hospital. Genes related to platelet activity were differentially expressed between hospitals.ConclusionsWe could not validate two TEP-based breast cancer classifiers in an independent validation cohort. The TEP protocol is sensitive to within-protocol variation and revision might be necessary before TEPs can be reconsidered for breast cancer detection.
| S-EPMC10070267 | biostudies-literature
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| S-EPMC10421922 | biostudies-literature
Project description:Colorectal cancer (CRC) is a major cause of cancer-associated death universally. Currently, the diagnosis, prognosis, and treatment monitoring of CRC mostly depends on endoscopy integrated with tissue biopsy. Recently, liquid biopsy has gained more and more attention in the area of molecular detection and monitoring of tumors due to ease of sampling, and its safe, non-invasive, and dynamic nature. Platelets, despite their role in hemostasis and thrombosis, are known to have an active, bifacial relationship with cancers. Platelets are the second most common type of cell in the blood and are one of the wealthy liquid biopsy biosources. These cells have the potential to absorb nucleic acids and proteins and modify their transcriptome with regard to external signals, which are termed tumor-educated platelets (TEPs). Liquid biopsies depend on TEPs' biomarkers which can be used to screen and also detect cancer in terms of prognosis, personalized treatment, monitoring, and prediction of recurrence. The value of TEPs as an origin of tumor biomarkers is relatively new, but platelets are commonly isolated using formidable and rapid techniques in clinical practice. Numerous preclinical researches have emphasized the potential of platelets as a new liquid biopsy biosource for detecting several types of tumors. This review discusses the potential use of platelets as a liquid biopsy for CRC.
| S-EPMC10685733 | biostudies-literature
Project description:Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
| S-EPMC6381325 | biostudies-literature
Project description:We report RNA-sequencing data of 779 blood platelet samples, including 402 tumor-educated platelet (TEP) samples collected from patients with non-small cell lung cancer (NSCLC). In addition, we report RNA-sequencing data of blood platelets isolated from 377 individuals without reported cancer, but not excluding individuals with inflammatory conditions. This dataset highlights the ability of TEP RNA-based 'liquid biopsy' diagnostics in patients with NSCLC.
2017-08-15 | GSE89843 | GEO
Project description:BackgroundTumor-educated platelets (TEPs) may enable blood-based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis.Materials and methodsThe TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein-protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real-time PCR (qRT-PCR) was applied to validate the role of DEGs in cancers.ResultsTEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early-stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT-PCR method.ConclusionThis study suggests that the 7-gene TEPs liquid-biopsy biomarkers may be used for cancer diagnosis and monitoring.
| S-EPMC8183939 | biostudies-literature
Project description:The increasing discoveries regarding the biology and functions of platelets in the last decade undoubtedly show that these cells are one of the most biotechnological human cells. This review summarizes new advances in platelet biology, functions, and new concepts of biotech-educated platelets that connect advanced biomimetic science to platelet-based additive manufacturing for tissue regeneration. As highly responsive and secretory cells, platelets could be explored to develop solutions that alter injured microenvironments through platelet-based synthetic biomaterials with instructive extracellular cues for morphogenesis in tissue engineering beyond tissue regeneration 2.0.
| S-EPMC7503652 | biostudies-literature
Project description:Platelets have been shown to promote the growth of tumors, including colorectal cancer. The RNA profile of tumor-educated platelets has the possibility for cancer diagnosis. We used RNA sequencing to identified the gene expression signature in platelets from colorectal cancer patients and healthy volunteers. We then verified the selected biomarkers from the RNA sequencing in a two-step case-control study using quantitative reverse-transcription polymerase chain reaction. We found that TIMP1 mRNA levels are higher in platelets from colorectal cancer patients than in platelets from healthy volunteers and patients with inflammatory bowel diseases. Additionally, TIMP1 mRNA expressed in platelets from colorectal cancer patients can be carried into colorectal cancer cells, where it promotes tumor growth in vivo and in vitro. These findings show that the TIMP1 mRNA in platelets is a potential independent diagnostic biomarker for colorectal cancer, and that platelets can carry RNAs into colorectal cancer cells to promote colorectal cancer development.
| S-EPMC6834400 | biostudies-literature
Project description:PurposeTumor-educated platelets (TEPs) are a promising liquid biopsy in many cancers. However, their role in renal cell carcinoma (RCC) is unknown. Thus, this study explored the diagnostic value of TEPs in RCC patients.MethodsPlatelets were prospectively collected from 24 RCC patients and 25 controls. RNA-seq was performed to identify the differentially expressed genes (DEGs) between RCC patients and controls. Besides, RNA-seq data of pan-cancer TEPs were downloaded and randomly divided into training and validation sets. A pan-cancer TEP model was developed in the training set using the support vector machine (SVM) and validated in the validation set and our RCC dataset. Finally, an RCC-based TEP model was developed and optimized through the SVM algorithms and recursive feature elimination (RFE) method.ResultTwo hundred three DEGs, 64 (31.5%) upregulated and 139 (68.5%) downregulated, were detected in the platelets of RCC patients compared with controls. The pan-cancer TEP model had a high accuracy in detecting cancer in the internal validation (training set, accuracy 98.8%, AUC: 0.999; validation set, accuracy 95.4%, AUC: 0.972; different tumor subtypes, accuracy 86.6%-96.1%, AUC: 0.952-1.000). However, the pan-cancer TEP model in the external validation had a scarce diagnostic value in RCC patients (accuracy 48.7%, AUC: 0.615). Therefore, to develop the RCC-based TEP model, the gene biomarkers mostly contributing to the model were selected using the RFE method. The RCC-based TEP model containing 68 gene biomarkers reached a diagnostic accuracy of 100% (AUC: 1.000) in the training set, 88.9% (AUC: 0.963) in the validation set, and 95.9% (AUC: 0.988) in the overall cohort.ConclusionTEPs could function as a minimally invasive blood biomarker in the detection of RCC.
| S-EPMC8936192 | biostudies-literature
Project description:Platelets are small anucleate cells that circulate in the blood and form thrombi. Tumor-educated platelets are the platelets derived from cancer patients. Although many have reported that tumor-educated platelets are associated with cancer-associated thrombosis, their function in this process is poorly understood. Here we first collect the clinical data from 100 different cancer patients, showing that cancer patients are in a hypercoagulable state. Our experiment shows that tumor-educated platelets from melanoma-burdened mouse models can migrate faster and longer, forming more clots (thrombus). However, the plasma from tumor mice can inhibit platelet migration. The RNA sequence profile of tumor-educated platelets shows that many genes associated with cell migration and cell skeleton expressed significantly higher. Our research offers a new insight into the tumor-educated platelets to better understand the thrombus formation.
| S-EPMC8907878 | biostudies-literature