Journal of Diagnostics Concepts & Practice >
Research progress on tumor-educated platelets in the diagnosis of common clinical tumors
Received date: 2024-05-22
Accepted date: 2024-08-05
Online published: 2025-02-25
Platelets not only play a crucial role in normal hemostasis and coagulation, but they are also closely associated with the occurrence, development, and metastasis of malignant tumors. Platelets are rich in RNA, which can be translated into proteins to perform various functions. Tumor cells can influence the RNA expression profiles of platelets in multiple ways. Platelets with altered RNA expression profiles due to tumor influence are referred to as tumor-educated platelets (TEPs). Research on TEPs in tumor diagnosis primarily focuses on two key areas. The first is transcriptomic sequencing of TEP RNA, followed by the analysis of sequencing results using bioinformatics methods. By integrating deep machine learning, novel algorithms and diagnostic models are developed to differentiate between cancer and non-cancer cases. The second area focuses on the expression levels of specific mRNA, microRNA, snRNA, snoRNA, and lncRNA in TEPs. The expression levels are analyzed and compared with non-cancer groups to evaluate their diagnostic efficacy. Currently, TEPs demonstrate significant diagnostic value in common clinical tumors such as lung cancer, liver cancer, breast cancer, ovarian cancer, and glioblastoma. Based on changes in the TEP mRNA profile, bioinformatics analysis shows an accuracy of 88%-91% for lung cancer diagnosis. Elevated mRNA expression of platelet ITGA2B in lung cancer patients results in an area under the curve (AUC) of 0.922, with a threshold value of 0.001759. TEP miRNA-122 levels are significantly elevated in liver cancer patients. At an optimal cutoff value of 4.46, its diagnostic performance achieves a sensitivity of 100.0% and a specificity of 93.3%. miRNA-21 also shows promising diagnostic performance. Bioinformatics analysis of platelet RNA profiles reveals that the TEP mRNA expression profile has an AUC of 0.72 and a sensitivity of 91% in distinguishing breast cancer patients from non-cancer patients. The ovarian cancer diagnostic model, TEPOC, based on 102 platelet RNAs, achieves an AUC of 0.93, outperforming CA125. The TEP mRNA expression profile distinguishes glioblastoma (GBM) from other brain metastases, multiple sclerosis patients, and healthy individuals, with AUCs of 0.84, 0.94, and 0.97, respectively. Due to platelets’ large amount, their ease of isolation, and their high diagnostic efficacy, TEPs show great promise as ideal biomarkers for tumor liquid biopsy, paving the way for clinical application.
Key words: Tumor-educated platelets; Tumor; Diagnosis
GAO Quancheng , HUANG Hui . Research progress on tumor-educated platelets in the diagnosis of common clinical tumors[J]. Journal of Diagnostics Concepts & Practice, 2024 , 23(05) : 550 -556 . DOI: 10.16150/j.1671-2870.2024.05.013
[1] | HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1):47-53. |
[2] | 沈佳莹, 蒋栋铭, 叶凌, 等. 2014-2019年浙江省舟山市岱山县居民恶性肿瘤发病和死亡分析[J]. 肿瘤, 2023, 43(2):97-105. |
SHEN J Y, JIANG D M, YE L, et al. Malignant tumor incidence and mortality in Daishan county,Zhoushan,Zhejiang Province from 2014 to 2019[J]. Tumor, 2023, 43(02):97-105. | |
[3] | CAMPANELLA R, GUARNACCIA L, CORDIGLIERI C, et al. Tumor-educated platelets and angiogenesis in glioblastoma: another brick in the wall for novel prognostic and targetable biomarkers, changing the vision from a localized tumor to a systemic pathology[J]. Cells, 2020, 9(2):294. |
[4] | LIU Y, ZHANG Y, DING Y, et al. Platelet-mediated tumor metastasis mechanism and the role of cell adhesion molecules[J]. Crit Rev Oncol Hematol, 2021, 167:103502. |
[5] | PLACKE T, ?RGEL M, SCHALLER M, et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells[J]. Cancer Res, 2012, 72(2):440-448. |
[6] | BEST M G, WESSELING P, WURDINGER T. Tumor-educated platelets as a noninvasive biomarker source for cancer detection and progression monitoring[J]. Cancer Res, 2018, 78(13):3407-3412. |
[7] | BEST M G, SOL N, KOOI I, et al. RNA-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics[J]. Cancer Cell, 2015, 28(5):666-676. |
[8] | BEST M G, SOL N, IN 'T VELD SGJG, et al. Swarm intelligence-enhanced detection of non-small-cell lung cancer using tumor-educated platelets[J]. Cancer Cell, 2017, 32(2):238-252.e9. |
[9] | XUE L, XIE L, SONG X, et al. Identification of potential tumor-educated platelets RNA biomarkers in non-small-cell lung cancer by integrated bioinformatical analysis[J]. J Clin Lab Anal, 2018, 32(7):e22450. |
[10] | XING S, ZENG T, XUE N, 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[J]. Int J Biol Sci, 2019, 15(9):1977-1992. |
[11] | DONG X, DING S, YU M, et al. Small nuclear RNAs (U1, U2, U5) in tumor-educated platelets are downregulated and act as promising biomarkers in lung cancer[J]. Front Oncol, 2020, 10:1627. |
[12] | 吴小婷. 肿瘤教育血小板miRNA表达谱在肝癌诊断中的应用研究[D]. 暨南大学, 2021. |
WU X T. Applicated study of tumor educated platelet miRNA expression profile in the diagnosis of liver cancer[D]. Jinan University, 2021. | |
[13] | 余恋雨, 王宇, 唱凯, 等. 肿瘤教育血小板源性miRNA-122和miRNA-21在肝癌早期诊断中的应用研究[J]. 国际检验医学杂志, 2022, 43(5):519-522. |
YU L Y, WANG Y, CHANG K, et al. Application of tumor educated platelets derived miRNA-122 and miRNA-21 in the early diagnosis of liver cancer[J]. Int J Lab Med, 2022, 43(05):519-522. | |
[14] | ZHU B, GU S, WU X, et al. Bioinformatics analysis of tumor-educated platelet microRNAs in patients with hepatocellular carcinoma[J]. Biosci Rep, 2021, 41(12):BSR20211420. |
[15] | ASGHAR S, WAQAR W, UMAR M, et al. Tumor educated platelets, a promising source for early detection of hepatocellular carcinoma: Liquid biopsy an alternative approach to tissue biopsy[J]. Clin Res Hepatol Gastroenterol, 2020, 44(6):836-844. |
[16] | WAQAR W, ASGHAR S, MANZOOR S. Platelets' RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules[J]. PLoS One, 2021, 16(9):e0256739. |
[17] | ZHAO X, CHEN G, WU Y, et al. TEP SNORD12B, SNORA63, and SNORD14E as novel biomarkers for hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC)[J]. Cancer Cell Int, 2024, 24(1):3. |
[18] | 汤凡凡. 肿瘤相关的血小板RNA用于肝癌诊断价值的研究[D]. 中南大学, 2022. |
TANG F F. Study on the diagnostic value of tumor-educated platelets RNA in liver cancer[D]. Central South University, 2022. | |
[19] | 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 传染病信息, 2020, 33(6):481-500. |
Bureau of Medical Administration, National Health Commission of the People′s Republic of China. Standardization for diagnosis and treatment of hepatocellular carcinoma (2019 edition)[J]. Infect dis info, 2020, 33(6):481-500. | |
[20] | LIEFAARD M C, LIPS E, BEST M, et al. 37PRNA signatures from tumor-educated platelets (TEP) enable detection of early-stage breast cancer[J]. Ann Oncol, 2019, 30(supp 3):iii13. |
[21] | LIEFAARD M C, MOORE K S, MULDER L, et al. Tumour-educated platelets for breast cancer detection: biological and technical insights[J]. Br J Cancer, 2023, 129(4):734. |
[22] | IN 'T VELD SGJG, ARKANI M, POST E, et al. Detection and localization of early- and late-stage cancers usi-ng platelet RNA[J]. Cancer Cell, 2022, 40(9):999-1009.e6. |
[23] | YAO B, QU S, HU R, et al. Delivery of platelet TPM3 mRNA into breast cancer cells via microvesicles enhances metastasis[J]. FEBS Open Bio, 2019, 9(12):2159-2169. |
[24] | BURCIAGA-HERNANDEZ L A, CUETO-VILLALOBOS C F, ORTEGA-PI?ON N, et al. Gene expression behavior of a set of genes in platelet and tissue samples from patients with breast cancer[J]. Int J Mol Sci, 2023, 24(9):8348. |
[25] | GAO Y, LIU C J, LI H Y, et al. Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study[J]. Protein Cell, 2023, 14(6):579-590. |
[26] | PIEK J, IN'T VELD S, BEST M, et al. EP457 Assessment of ovarian tumors with tumor educated platelets(TEP)[J]. Int J Gynecol Cancer, 2019, 29: A291-A292. |
[27] | SOL N, IN 'T VELD SGJG, VANCURA A, et al. Tumor-educated platelet rna for the detection and (pseudo)progression monitoring of glioblastoma[J]. Cell Rep Med, 2020, 1(7):100101. |
[28] | WANG H, WEI X, WU B, et al. Tumor-educated platelet miR-34c-3p and miR-18a-5p as potential liquid biopsy biomarkers for nasopharyngeal carcinoma diagnosis[J]. Cancer Manag Res, 2019, 11:3351-3360. |
[29] | LIU T, WANG X, GUO W, et al. RNA sequencing of tumor-educated platelets reveals a three-gene diagnostic signature in esophageal squamous cell carcinoma[J]. Front Oncol, 2022, 12:824354. |
[30] | LIU Y, QIAN J, LI D Z, et al. TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer[J]. Aging (Albany NY), 2019, 11(20):8998-9012. |
[31] | XU L, LI X, LI X, et al. RNA profiling of blood platelets noninvasively differentiates colorectal cancer from healthy donors and noncancerous intestinal diseases: a retrospective cohort study[J]. Genome Med, 2022, 14(1):26. |
[32] | YE B, LI F, CHEN M, et al. A panel of platelet-associa-ted circulating long non-coding RNAs as potential biomarkers for colorectal cancer[J]. Genomics, 2022, 114(1):31-37. |
[33] | TABAEIAN S P, ESHKIKI Z S, DANA F, et al. Evaluation of tumor-educated platelet long non-coding RNAs (lncRNAs) as potential diagnostic biomarkers for colorectal cancer[J]. J Cancer Res Ther, 2024, 20(5):1453-1458. |
[34] | CAMPOLO F, SESTI F, FEOLA T, et al. Platelet-derived circRNAs signature in patients with gastroenteropanc-retic neuroendocrine tumors[J]. J Transl Med, 2023, 21(1):548. |
[35] | BRAVACCINI S, BOLDRIN E, GURIOLI G, et al. The use of platelets as a clinical tool in oncology: opportunities and challenges[J]. Cancer Lett, 2024, 607:217044. |
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