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      A narrative review for platelets and their RNAs in cancers: New concepts and clinical perspectives

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          Abstract

          Recent years have witnessed a growing body of evidence suggesting that platelets are involved in several stages of the metastatic process via direct or indirect interactions with cancer cells, contributing to the progression of neoplastic malignancies. Cancer cells can dynamically exchange components with platelets in and out of blood vessels, and directly phagocytose platelets to hijack their proteome, transcriptome, and secretome, or be remotely regulated by metabolites or microparticles released by platelets, resulting in phenotypic, genetic, and functional modifications. Moreover, platelet interactions with stromal and immune cells in the tumor microenvironment lead to alterations in their components, including the ribonucleic acid (RNA) profile, and complicate the impact of platelets on cancers. A deeper understanding of the roles of platelets and their RNAs in cancer will contribute to the development of anticancer strategies and the optimization of clinical management. Encouragingly, advances in high-throughput sequencing, bioinformatics data analysis, and machine learning have allowed scientists to explore the potential of platelet RNAs for cancer diagnosis, prognosis, and guiding treatment. However, the clinical application of this technique remains controversial and requires larger, multicenter studies with standardized protocols. Here, we integrate the latest evidence to provide a broader insight into the role of platelets in cancer progression and management, and propose standardized recommendations for the clinical utility of platelet RNAs to facilitate translation and benefit patients.

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          Current and future perspectives of liquid biopsies in genomics-driven oncology

          Precision oncology seeks to leverage molecular information about cancer to improve patient outcomes. Tissue biopsy samples are widely used to characterize tumours but are limited by constraints on sampling frequency and their incomplete representation of the entire tumour bulk. Now, attention is turning to minimally invasive liquid biopsies, which enable analysis of tumour components (including circulating tumour cells and circulating tumour DNA) in bodily fluids such as blood. The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence. However, the analytical validity and clinical utility of liquid biopsies must be rigorously demonstrated before this potential can be realized.
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            RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

            Summary Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based “liquid biopsies”.
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              Role of platelets and platelet receptors in cancer metastasis

              The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells immediately activate platelets to form a permissive microenvironment. Platelets protect tumor cells from shear forces and assault of NK cells, recruit myeloid cells by secretion of chemokines, and mediate an arrest of the tumor cell platelet embolus at the vascular wall. Subsequently, platelet-derived growth factors confer a mesenchymal-like phenotype to tumor cells and open the capillary endothelium to expedite extravasation in distant organs. Finally, platelet-secreted growth factors stimulate tumor cell proliferation to micrometastatic foci. This review provides a synopsis on the current literature on platelet-mediated effects in cancer metastasis and particularly focuses on platelet adhesion receptors and their role in metastasis. Immunoreceptor tyrosine-based activation motif (ITAM) and hemi ITAM (hemITAM) comprising receptors, especially, glycoprotein VI (GPVI), FcγRIIa, and C-type lectin-like-2 receptor (CLEC-2) are turned in the spotlight since several new mechanisms and contributions to metastasis have been attributed to this family of platelet receptors in the last years.
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                Author and article information

                Contributors
                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MD
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                30 December 2022
                30 December 2022
                : 101
                : 52
                : e32539
                Affiliations
                [a ] Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
                [b ] Department of Laboratory Medicine, Xiping Community Health Service Center of Longquanyi District Chengdu City, Chengdu, China.
                Author notes
                * Correspondence: Juan Zhang, Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32# West Second Section, First Ring Road, Qingyang District, Chengdu City, Sichuan Province 610072, China (e-mail: zhangjuan82@ 123456126.com ).
                Article
                00066
                10.1097/MD.0000000000032539
                9803462
                36596034
                3be14723-0a90-438a-bd2c-633458e59a72
                Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 October 2022
                : 11 December 2022
                : 12 December 2022
                Categories
                5700
                Research Article
                Narrative Review
                Custom metadata
                TRUE

                diagnostics,platelet-educated tumor cells,rna,tumor microenvironment,tumor-educated platelets (teps)

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