The Importance of Different Types of RNA Molecules in Platelets for the Diagnosis and Monitoring of Tumor Progression

Document Type : Review Article

Authors

1 MSc, Department of Hematology and Blood Banking, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

2 PhD Student, Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

3 MSc, Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

4 PhD, Department of Molecular Imaging, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, AND Regenerative Medicine Group (REMED), Universal Scientific Education & Research Network (USERN), Tehran, Iran

Abstract

Background: Platelets are multi-purpose cell parts circulating abundantly in the blood and can be educated by their environment. Platelets actively change their nucleic acid content in response to local and systemic pathological conditions and can play a role in cancer development and progression by supporting the growth, survival, and dissemination of tumor cells. In the current study, the importance of RNAs in platelets -as less invasive biomarkers- for early diagnosis of cancers and also for tracking tumor progression has been investigated.
Methods: Reliable scientific databases such as PubMed, Web of Science, Scopus, and Google Scholar were used to gather relevant articles for this review study.
Findings: The nucleic acid content of platelets is provided both by their generator (megakaryocyte) and mediators such as cancer cells. Different types of coding and non-coding RNA make up the nucleic acid content of platelets, and cancer cells affect platelet RNA content in tumor-educated platelets through direct and indirect pathways.
Conclusion: Advances in molecular technologies and subsequent deep insight into the profile of tumor-educated platelet RNAs, including the discovery of small and longer regulatory RNAs, have enabled the analysis of tumor-educated platelet RNA profiles as a new source for early cancer diagnosis.

Highlights

Sima Kalantari: Google Scholar

Keywords

Main Subjects


  1. van Der Pol Y, Mouliere F. Toward the early detection of cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA. Cancer Cell 2019; 36(4): 350-68.
  2. Mader S, Pantel K. Liquid biopsy: current status and future perspectives. Oncol Res Treat 2017; 40(7-8): 404-8.
  3. Junqueira-Neto S, Batista IA, Costa JL, Melo SA. Liquid biopsy beyond circulating tumor cells and cell-free DNA. Acta Cytol 2019; 63(6): 479-88.
  4. Heitzer E, Haque IS, Roberts CE, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet 2019; 20(2): 71-88.
  5. Pourshams A, Kazemi B, Kalantari S. A review of the etiology and biomarkers of pancreatic cancer, with emphasis on the role of diabetes: review article. Tehran Univ Med J 2018; 75(11): 773-8.
  6. Zhang Q, Song X, Song X. Contents in tumor-educated platelets as the novel biosource for cancer diagnostics. Front Oncol 2023; 13: 1165600.
  7. Kalantari S, Pourshams A, Roudi R, Zali H, Bandehpour M, Kalantari A, et al. Identification of potential common molecular factors of pancreatic cancer and diabetes mellitus using microarray data analysis combined with bioinformatics techniques and experimental validation. Biomed Biotechnol Res J 2021; 5(3): 286-94.
  8. Kalantari S, Kazemi B, Roudi R, Zali H, D'Angelo A, Mohamadkhani A, et al. RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients. Cell Biol Int 2023; 47(1): 238-49.
  9. Best M, Vancura A, Wurdinger T. Platelet RNA as a circulating biomarker trove for cancer diagnostics. J Thromb Haemost 2017; 15(7): 1295-306.
  10. Economopoulou P, Kotsantis I, Kyrodimos E, Lianidou E, Psyrri A. Liquid biopsy: an emerging prognostic and predictive tool in head and neck squamous cell carcinoma (HNSCC). Focus on circulating tumor cells (CTCs). Oral Oncol 2017; 74: 83-9.
  11. Di Meo A, Bartlett J, Cheng Y, Pasic MD, Yousef GM. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Mol Cancer 2017; 16(1): 80.
  12. Gorgannezhad L, Umer M, Islam MN, Nguyen NT, Shiddiky MJ. Circulating tumor DNA and liquid biopsy: opportunities, challenges, and recent advances in detection technologies. Lab Chip 2018; 18(8): 1174-96.
  13. Feller SM, Lewitzky M. Hunting for the ultimate liquid cancer biopsy-let the TEP dance begin. Cell Commun Signal 2016; 14(1): 24.
  14. Wurdinger T, In ‘t Veld SG, Best MG. Platelet RNA as pan-tumor biomarker for cancer detection. Cancer Res 2020; 80(7): 1371-3.
  15. In 't Veld SGJG, Wurdinger T. Tumor-educated platelets. Blood 2019; 133(22): 2359-64.
  16. Bottsford-Miller J, Choi HJ, Dalton HJ, Stone RL, Cho MS, Haemmerle M, et al. Differential platelet levels affect response to taxane-based therapy in ovarian cancer. Clin Cancer Res 2015; 21(3): 602-10.
  17. Wang R, Stone RL, Kaelber JT, Rochat RH, Nick AM, Vijayan KV, et al. Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer. Proc Natl Acad Sci U S A 2015; 112(46): 14266-71.
  18. Kamińska J, Koper OM, Mantur M, Matowicka-Karna J, Sawicka-Powierza J, Sokołowski J, et al. Does thrombopoiesis in multiple myeloma patients depend on the stage of the disease? Adv Med Sci 2014; 59(2): 166-71.
  19. Haemmerle M, Stone RL, Menter DG, Afshar-Kharghan V, Sood AK. The platelet lifeline to cancer: challenges and opportunities. Cancer Cell 2018; 33(6): 965-83.
  20. Best MG, Wesseling P, Wurdinger T. Tumor-educated platelets as a noninvasive biomarker source for cancer detection and progression monitoring. Cancer Res 2018; 78(13): 3407-12.
  21. D’Ambrosi S, Nilsson RJ, Wurdinger T. Platelets and tumor-associated RNA transfer. Blood 2021; 137(23): 3181-91.
  22. Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, et al. RNA-Seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell 2015; 28(5): 666-76.
  23. Dib PRB, Quirino-Teixeira AC, Merij LB, Pinheiro MBM, Rozini SV, Andrade FB, et al. Innate immune receptors in platelets and platelet-leukocyte interactions. J Leukoc Biol 2020; 108(4): 1157-82.
  24. Saha B, Mathur T, Handley KF, Hu W, Afshar-Kharghan V, Sood AK, et al. OvCa-Chip microsystem recreates vascular endothelium-mediated platelet extravasation in ovarian cancer. Blood Adv 2020; 4(14): 3329-42.
  25. Cimmino G, Tarallo R, Nassa G, De Filippo MR, Giurato G, Ravo M, et al. Activating stimuli induce platelet microRNA modulation and proteome reorganisation. Thromb Haemost 2015; 114(1): 96-108.
  26. Sabrkhany S, Kuijpers MJ, Knol JC, Damink SWO, Dingemans AMC, Verheul HM, et al. Exploration of the platelet proteome in patients with early-stage cancer. J Proteomics 2018; 177: 65-74.
  27. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 2007; 110(6): 1723-9.
  28. Qi C, Li B, Guo S, Wei B, Shao C, Li J, et al. P-Selectin-mediated adhesion between platelets and tumor cells promotes intestinal tumorigenesis in ApcMin/+ mice. Int J Biol Sci 2015; 11(6): 679-87.
  29. Olsson AK, Cedervall J. The pro-inflammatory role of platelets in cancer. Platelets 2018; 29(6): 569-73.
  30. Cho MS, Noh K, Haemmerle M, Li D, Park H, Hu Q, et al. Role of ADP receptors on platelets in the growth of ovarian cancer. Blood 2017; 130(10): 1235-42.
  31. Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo. Int J Cancer 2015; 136(2): 462-75
  32. Alhasan AA, Izuogu OG, Al-Balool HH, Steyn JS, Evans A, Colzani M, et al. Circular RNA enrichment in platelets is a signature of transcriptome degradation. Blood 2016; 127(9): e1-11.
  33. Schubert S, Weyrich AS, Rowley JW. A tour through the transcriptional landscape of platelets. Blood 2014; 124(4): 493-502.
  34. Laffont B, Corduan A, Rousseau M, Duchez AC, Lee CHC, Boilard E, et al. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost 2016; 115(2): 311-23.
  35. Rossaint J, Kühne K, Skupski J, Van Aken H, Looney MR, Hidalgo A, et al. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun 2016; 7: 13464.
  36. Kirschbaum M, Karimian G, Adelmeijer J, Giepmans BN, Porte RJ, Lisman T. Horizontal RNA transfer mediates platelet-induced hepatocyte proliferation. Blood 2015; 126(6): 798-806.
  37. Clancy L, Freedman J. The role of circulating platelet transcripts. J Thromb Haemost 2015; 13(Suppl 1): S33-9.
  38. Nilsson RJA, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, et al. Blood platelets contain tumor-derived RNA biomarkers. Blood 2011; 118(13): 3680-3.
  39. Nilsson RJA, Karachaliou N, Berenguer J, Gimenez-Capitan A, Schellen P, Teixido C, et al. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget 2016; 7(1): 1066-75.
  40. Zarà M, Guidetti GF, Camera M, Canobbio I, Amadio P, Torti M, et al. Biology and role of extracellular vesicles (EVs) in the pathogenesis of thrombosis. Int J Mol Sci 2019; 20(11): 2840.
  41. Plantureux L, Mège D, Crescence L, Carminita E, Robert S, Cointe S, et al. The interaction of platelets with colorectal cancer cells inhibits tumor growth but promotes metastasis. Cancer Res 2020; 80(2): 291-303.
  42. Osaki M, Okada F. Exosomes and their role in cancer progression. Yonago Acta Med 2019; 62(2): 182-90.
  43. Londin ER, Hatzimichael E, Loher P, Edelstein L, Shaw C, Delgrosso K, et al. The human platelet: strong transcriptome correlations among individuals associate weakly with the platelet proteome. Biol Direct 2014; 9: 3.
  44. Yao B, Qu S, Hu R, Gao W, Jin S, Ju J, et al. Delivery of platelet TPM3 mRNA into breast cancer cells via microvesicles enhances metastasis. FEBS Open Bio 2019; 9(12): 2159-69.
  45. Yang L, Jiang Q, Li DZ, Zhou X, Yu DS, Zhong J. TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer. Aging (Albany NY) 2019; 11(20): 8998-9012.
  46. Calverley DC, Phang TL, Choudhury QG, Gao B, Oton AB, Weyant MJ, et al. Significant downregulation of platelet gene expression in metastatic lung cancer. Clin Transl Sci 2010; 3(5): 227-32.
  47. Wiyarta E, Nugraha DA, Ramadani MI, Gustya GF, Ammar MF, Edwar HD, et al. Clinical utility and diagnostic value of tumor-educated platelets in lung cancer: a systematic review and meta-analysis. Front Oncol 2023; 13: 1201713.
  48. Best MG, Sol N, GJG S, Vancura A, Muller M, Niemeijer ALN, et al. Swarm intelligence-enhanced detection of non-small-cell lung cancer using tumor-educated platelets. Cancer Cell 2017; 32(2): 238-52.
  49. Takemoto A, Okitaka M, Takagi S, Takami M, Sato S, Nishio M, et al. A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis. Sci Rep 2017; 7: 42186
  50. Tjon-Kon-Fat LA, Lundholm M, Schröder M, Wurdinger T, Thellenberg-Karlsson C, Widmark A, et al. Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients. Prostate 2018; 78(1): 48-53.
  51. Sheng M, Dong Z, Xie Y. Identification of tumor-educated platelet biomarkers of non-small-cell lung cancer. Onco Targets Ther 2018; 11: 8143-51.
  52. Luo CL, Xu ZG, Chen H, Ji J, Wang YH, Hu W, et al. LncRNAs and EGFRvIII sequestered in TEPs enable blood-based NSCLC diagnosis. Cancer Manag Res 2018; 10: 1449-59.
  53. Tímár J, Tóvári J, Rásó E, Mészáros L, Bereczky B, Lapis K. Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology 2005; 69(3): 185-201.
  54. Park CK, Kim JE, Kim MS, Kho BG, Park HY, Kim TO, et al. Feasibility of liquid biopsy using plasma and platelets for detection of anaplastic lymphoma kinase rearrangements in non-small cell lung cancer. J Cancer Res Clin Oncol 2019; 145(8): 2071-82.
  55. Xing S, Zeng T, Xue N, He Y, Lai YZ, Li HL, et al. Development and validation of tumor-educated blood platelets integrin alpha 2b (ITGA2B) RNA for diagnosis and prognosis of non-small-cell lung cancer through RNA-seq. Int J Biol Sci 2019; 15(9): 1977-92.
  56. Liu L, Song X, Li X, Xue L, Ding S, Niu L, et al. A three-platelet mRNA set: MAX, MTURN and HLA-B as biomarker for lung cancer. J Cancer Res Clin Oncol 2019; 145(11): 2713-23.
  57. Heinhuis KM, In’t Veld SG, Dwarshuis G, Van Den Broek D, Sol N, Best MG, et al. RNA-sequencing of tumor-educated platelets, a novel biomarker for blood-based sarcoma diagnostics. Cancers (Basel) 2020; 12(6): 1372.
  58. 58- Fejes Z, Póliska S, Czimmerer Z, Káplár M, Penyige A, Szabó GG, et al. Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb Haemost 2017; 117(3): 529-42.
  59. Koppers-Lalic D, Hackenberg M, Bijnsdorp IV, van Eijndhoven MA, Sadek P, Sie D, et al. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep 2014; 8(6): 1649-58.
  60. Gidlöf O, van der Brug M, Öhman J, Gilje P, Olde B, Wahlestedt C, et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 2013; 121(19): 3908-17, S1-26.
  61. Laffont B, Corduan A, Plé H, Duchez AC, Cloutier N, Boilard E, et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood 2013; 122(2): 253-61.
  62. Liang H, Yan X, Pan Y, Wang Y, Wang N, Li L,
    et al. MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3. Mol Cancer 2015; 14(1): 58.
  63. Anene C, Graham AM, Boyne J, Roberts W. Platelet microparticle delivered microRNA-Let-7a promotes the angiogenic switch. Biochim Biophys Acta Mol Basis Dis 2018; 1864(8): 2633-43.
  64. Michael JV, Wurtzel JG, Mao GF, Rao AK, Kolpakov MA, Sabri A, et al. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 2017; 130(5): 567-80.
  65. Angenieux C, Maitre B, Eckly A, Lanza F, Gachet C, de la Salle H. Time-dependent decay of mRNA and ribosomal RNA during platelet aging and its correlation with translation activity. PLoS One 2016; 11(1): e0148064.
  66. Wang H, Wei X, Wu B, Su J, Tan W, Yang K. Tumor-educated platelet miR-34c-3p and miR-18a-5p as potential liquid biopsy biomarkers for nasopharyngeal carcinoma diagnosis. Cancer Manag Res 2019; 11: 3351-60.
  67. Dong X, Ding S, Yu M, Niu L, Xue L, Zhao Y, et al. Small nuclear RNAs (U1, U2, U5) in tumor-educated platelets are downregulated and act as promising biomarkers in lung cancer. Front Oncol 2020; 10: 1627.
  68. D’ambrosi S, Visser A, Antunes-Ferreira M, Poutsma A, Giannoukakos S, Sol N, et al. The analysis of platelet-derived circRNA repertoire as potential diagnostic biomarker for non-small cell lung cancer. Cancers 2021; 13(18): 4644.
  69. Li X, Liu L, Song X, Wang K, Niu L, Xie L, et al. TEP linc-GTF2H2-1, RP3-466P17. 2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction. J Cancer Res Clin Oncol 2021; 147(6): 1609-22.
  70. Dong X, Song X, Ding S, Yu M, Shang X, Wang K, et al. Tumor-educated platelet SNORD55 as a potential biomarker for the early diagnosis of non‐small cell lung cancer. Thorac Cancer 2021; 12(5): 659-66.
  71. Wei J, Meng X, Wei X, Zhu K, Du L, Wang H. Down-regulated lncRNA ROR in tumor-educated platelets as a liquid-biopsy biomarker for nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2023; 149(8): 4403-9.
  72. Ye B, Li F, Chen M, Weng Y, Qi C, Xie Y, et al. A panel of platelet-associated circulating long non-coding RNAs as potential biomarkers for colorectal cancer. Genomics 2022; 114(1): 31-7.
  73. Ehya F, Kalantari S, Bandehpour M, Kazemi B. Preliminary Information of Iranian Lizard Leishmania Promastigote Transcriptome Sequencing by Next-Generation Sequencing (NGS) Method. Iran J Parasitol 2023; 18(3): 362-8.
  74. Liu H, Begik O, Lucas MC, Ramirez JM, Mason CE, Wiener D, et al. Accurate detection of m6A RNA modifications in native RNA sequences. Nat Commun 2019; 10(1): 4079.

Parker MT, Knop K, Sherwood AV, Schurch NJ, Mackinnon K, Gould PD, et al. Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and m6A modification. Elife 2020; 9: e49658.