Tumor-educated Platelets Research Articles

Platelet-Derived Microvesicles Promote Selective Cell Viability in Hepatocellular Carcinoma: Differences in Properties between Normal Platelets and Tumor Educated Platelets

Tumor cells educate platelets by modulating their RNA profiles and phenotypes. These platelets are termed "tumor educated platelets: TEPs", and this concept is widely accepted. We have previously reported that platelets are activated in microvessels within liver tumors, leading to the progression of hepatocellular carcinoma (HCC). When platelets are activated, platelet-derived microvesicles (PDMV) containing platelet-derived nucleic acids and proteins are released. The contents in these are known to vary depending on the various pathological conditions of the host. It is generally believed that when cells take up extracellular vesicles, they are affected by the action of the encapsulated substances. However, it is still unclear what biological properties of PDMV are released by TEPs and how they are involved in carcinogenesis. We hypothesized that the release of PDMV by activated platelets in liver tissue and the uptake of its contents by normal hepatocytes and HCC cells may be involved in the progression of hepatocarcinogenesis, and we analyzed their role in carcinogenesis. The rat HCC model was prepared according to the Solt-Farber protocol. Briefly, male F344 rats were injected intraperitoneally with diethylnitrosamine at 4 weeks of age, then fed a powdered diet containing 2-acetylaminofluorene to induce liver damage, followed by partial hepatectomy. The rats were then kept under normal conditions for more than one month. Abdominal ultrasonography was performed on rats, and those with obvious tumors with a diameter of 2 mm or more were used for the experiments. Peripheral blood was collected from the tail veins of normal rats or HCC model rats, and platelets were isolated. The platelets were labeled with the fluorescent substance CMRA, activated in vitro with thrombin, and the PDMV in the supernatant was collected by polyethylene glycol precipitation and used as CMRA-labeled PDMV in the experiments. When PDMV was added to primary cultured rat hepatocytes and cultured for 24 hours, fluorescence was observed in the hepatocytes. The fluorescence was also observed in hepatocytes in the portal region of liver tissue collected 24 hours after injection of CMRA-labeled PDMV from the mesenteric vein of rats. These indicate that PDMV released into the liver tissue is taken up by hepatocytes. Peripheral blood platelets from normal rats or HCC model rats were isolated and PDMV was purified from each (N-PDMV and HCC-PDMV). These PDMVs were added to cultures of normal rat hepatocytes and hepatocellular carcinoma cell lines to analyze their effects on cell survival. N-PDMV did not affect the viability of normal hepatocytes, but mildly enhanced the survival of HCC cells. On the other hand, HCC-PDMV inhibited the viability of normal hepatocytes, but promoted viability of HCC cells more strongly than N-PDMV. These results indicate that the contents of PDMV differ between normal and HCC rats, and in particular that PDMV from rats with HCC is taken up by normal and HCC cells and is associated with selective survival of HCC cells.

Liquid biopsy-from bench to bedside.

Over the last decade, molecular markers have become an integral part in the management of Central Nervous System (CNS) tumors. Somatic mutations that identify and prognosticate tumors are also detected in the bio-fluids especially the serum and CSF; the sampling of which is known as liquid biopsy (LB). These tumor-derived biomarkers include plasma circulating tumor cells (CTCs), cell-free DNA (cf/ctDNAs), circulating cell-free microRNAs (cfmiRNAs), circulating extracellular vesicles, or exosomes (EVs), proteins, and tumor educated platelets. Established in the management of other malignancies, liquid biopsy is becoming an important tool in the management of CNS tumors as well. This review presents a snapshot of the current state of LB research its potential and the possible pitfalls.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Application of tumor-educated platelets as new fluid biopsy markers in various tumors.

The incidence of malignant tumors is increasing year by year. Early detection and diagnosis of malignant tumors can improve the prognosis of patients and prolong their life. Pathological biopsy is the current gold standard for diagnosis, but the results of pathological biopsy are affected by the sampling site and cannot fully reflect the nature of the disease. Moreover, the invasive nature of pathological biopsy limits repeated detection. Liquid biopsies are non-invasive and can be used for early detection and monitoring of tumors, which considered to represent a promising tool. Platelets make themselves to be one of the richest liquid biopsy sources by the capacity to take up proteins and nucleic acids and alter their megakaryocyte-derived transcripts and proteins in response to external signals, which are called tumor-educated platelets (TEPs). In this article, we will review the application of tumor-educated platelets in various malignancies (nasopharyngeal carcinoma, prostate cancer, lung cancer, glioblastoma, colorectal cancer, pancreas cancer, ovarian cancer, sarcoma, breast cancer and hepatocellular carcinoma) and provide theoretical basis for the research of TEPs in tumor diagnosis, monitoring and treatment.

BLOODPAC: Collaborating to chart a path towards blood-based screening for early cancer detection.

BLOODPAC: Collaborating to chart a path towards blood-based screening for early cancer detection.

New insights of liquid biopsy in ovarian cancer

Through the development of new analysis technologies, many issues regarding the approach to tumoral diseases have been elucidated. With analytical assays developed in the last years, various omics technologies have evolved in such a manner that the characteristics of tumor cells and products can be evaluated (assessed) in the bloodstream of cancer patients at different times. Ovarian Cancer (OC) is one of the most difficult to diagnose umors, with low survival rates due to the high heterogeneity of these diseases that are distinct in terms of etiology and molecular characteristics, but which simply share an anatomical appearance. Recent findings have indicated that several types of ovarian cancer classified into different histotypes are in fact derived from non-ovarian issues and share few molecular similarities. Within this context, ovarian cancer screening and diagnosis can be made through the evaluation of circulating tumor cells in peripheral blood using liquid biopsy technologies. Advances in the study of various molecules analyzed by liquid biopsy have shown that elucidation of intratumoural and intertumoural heterogeneity and spatial and temporal tumor evolution could be traced by serial blood tests rather than by histopathological analyses of tissue samples from a primary tumor. Therefore, evaluation of some molecules such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating cell-free RNA (non-coding and mRNA, extracellular vesicles), tumor-educated platelets or different miRNAs using liquid biopsy could lead to improvement of patient management.

Application progress of liquid biopsy in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors globally. Guiding the individualized treatment of GC is the focus of research. Obtaining representative biological samples to study the biological characteristics of GC is the focus of diagnosis and treatment of GC. Liquid biopsy technology can use high-throughput sequencing technology to detect biological genetic information in blood. Compared with traditional tissue biopsy, liquid biopsy can determine the dynamic changes of tumor. As a noninvasive auxiliary diagnostic method, liquid biopsy can provide diagnostic and prognostic information concerning the progression of the disease. Liquid biopsy includes circulating tumor cells, circulating tumor DNA, circulating tumor RNA, tumor educated platelets, exosomes, and cytokines. This article describes the classification of liquid biopsy and its application value in the occurrence, development, and therapeutic efficacy of GC.

Down-regulated lncRNA ROR in tumor-educated platelets as a liquid-biopsy biomarker for nasopharyngeal carcinoma

PurposesTo evaluate the diagnostic value of tumor-educated platelets (TEP) lncRNA ROR for nasopharyngeal carcinoma (NPC).MethodsQuantitative real-time PCR was used to determine the expression level of TEP lncRNA ROR in NPC patients (n = 50) as compared to normal subjects (n = 33). The ROC curve analysis was performed to assess the diagnostic value of TEP lncRNA ROR for NPC. Correlations between TEP lncRNA ROR and clinical parameters were further analyzed.ResultsThe median of TEP lncRNA ROR was significantly lower in NPC patients than that in normal subjects (0.0209 vs 0.0610, p = 0.0019), while no significant difference was found in plasma lncRNA ROR. ROC analysis showed that TEP lncRNA ROR had a sensitivity of 60%, specificity of 70%, and accuracy of 63.9% in diagnosing NPC, and the area under ROC curve (AUC) was 0.70. The expression level of TEP lncRNA ROR in NPC showed no significant difference among different TNM stages. However, low level of TEP lncRNA ROR correlated well with positive Epstein–Barr virus (EBV) DNA (kappa value = 0.314, p = 0.06), TEP lncRNA ROR and EBV DNA had similar diagnostic positive rate (58.3%) for NPC, and the combination of TEP lncRNA ROR and EBV DNA increased the positive rate to 74%.ConclusionThe expression level of TEP lncRNA ROR was down-regulated in NPC and the diagnostic value of TEP lncRNA ROR was similar to EBV DNA. Our study indicated that TEP lncRNA ROR might serve as a novel type of liquid biopsy biomarker in diagnosis of NPC patients.

Liquid Biopsy Analysis as a Tool for TKI-Based Treatment in Non-Small Cell Lung Cancer.

The treatment of non-small cell lung cancer (NSCLC) has recently evolved with the introduction of targeted therapy based on the use of tyrosine kinase inhibitors (TKIs) in patients with certain gene alterations, including EGFR, ALK, ROS1, BRAF, and MET genes. Molecular targeted therapy based on TKIs has improved clinical outcomes in a large number of NSCLC patients with advanced disease, enabling significantly longer progression-free survival (PFS). Liquid biopsy is an increasingly popular diagnostic tool for treating TKI-based NSCLC. The studies presented in this article show that detection and analysis based on liquid biopsy elements such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, and/or tumor-educated platelets (TEPs) can contribute to the appropriate selection and monitoring of targeted therapy in NSCLC patients as complementary to invasive tissue biopsy. The detection of these elements, combined with their molecular analysis (using, e.g., digital PCR (dPCR), next generation sequencing (NGS), shallow whole genome sequencing (sWGS)), enables the detection of mutations, which are required for the TKI treatment. Despite such promising results obtained by many research teams, it is still necessary to carry out prospective studies on a larger group of patients in order to validate these methods before their application in clinical practice.

Liquid biopsy in lung cancer management.

Liquid biopsy is a promising tool for a better cancer management and currently opens perspectives for several clinical applications, such as detection of mutations when the analysis from tissue is not available, monitoring tumor mutational burden and prediction of targeted therapy response. These characteristics validate liquid biopsy analysis as a strong cancer biomarkers source with high potential for improving cancer patient's evolution. Compared to classical biopsy, liquid biopsy is a minimal invasive procedure, and it allows the real-time monitoring of treatment response. Considering that lung cancer is the most common cause of cancer-associated death worldwide and that only 15-19% of the lung cancer patients survive five years after diagnosis, there is an important interest in improving its management. Like in other types of solid cancers, lung cancer could benefit from liquid biopsy through a simple peripheral blood sample as tumor-related biomarkers, such as circulating tumor cells (CTCs), cell-free nucleic acids (cfNA) [cell-free ribonucleic acid (cfRNA) and cell-free deoxyribonucleic acid (cfDNA)], exosomes and tumor-educated platelets (TEPs) may shed into circulation because of necrosis or in an active manner. More, the detection and analysis of these biomarkers could lead to a better understanding of oncological diseases like lung cancer. The better the tumor profile is established; the better management is possible. However, this approach has currently some limitations, such as low cfNA concentration or low count of CTCs that might be overcome by improving the actual methods and technologies.

Detection and localization of early- and late-stage cancers using platelet RNA.

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Emerging roles of platelets in cancer biology and their potential as therapeutic targets.

The main role of platelets is to control bleeding and repair vascular damage via thrombosis. They have also been implicated to promote tumor metastasis through platelet-tumor cell interactions. Platelet-tumor cell interactions promote tumor cell survival and dissemination in blood circulation. Tumor cells are known to induce platelet activation and alter platelet RNA profiles. Liquid biopsies based on tumor-educated platelet biomarkers can detect tumors and correlate with prognosis, personalized therapy, treatment monitoring, and recurrence prediction. Platelet-based strategies for cancer prevention and tumor-targeted therapy include developing drugs that target platelet receptors, interfere with the release of platelet particles, inhibit platelet-specific enzymes, and utilize platelet-derived “nano-platelets” as a targeted drug delivery platform for tumor therapy. This review elaborates on platelet-tumor cell interactions and the molecular mechanisms and discusses future research directions for platelet-based liquid biopsy techniques and platelet-targeted anti-tumor strategies.

Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code.

Simple SummaryPatients with ovarian cancer have a very poor chance of long-term survival, usually due to advanced disease at the time of diagnosis. Emerging evidence suggests that extracellular vesicles contain noncoding RNAs such as microRNAs, piwiRNAs, circular RNAs, and long noncoding RNAs, with regulatory effects on ovarian cancer. In this review, we focus on ovarian cancer-associated circular RNA shuttled by extracellular vesicles as mediators of cancer progression and novel biomarkers in liquid biopsy. We propose a circular-RNA–microRNA-mRNA code that can reveal the regulatory network created by extracellular vesicles, noncoding RNAs, and mRNAs in ovarian cancer. Future research in this field will help to identify novel diagnostic biomarkers and druggable therapeutic targets, which will ultimately benefit patients.Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in females worldwide. OC is frequently diagnosed at an advanced stage due to a lack of specific symptoms and effective screening tests, resulting in a poor prognosis for patients. Age, genetic alterations, and family history are the major risk factors for OC pathogenesis. Understanding the molecular mechanisms underlying OC progression, identifying new biomarkers for early detection, and discovering potential targets for new drugs are urgent needs. Liquid biopsy (LB), used for cancer detection and management, consists of a minimally invasive approach and practical alternative source to investigate tumor alterations by testing extracellular vesicles (EVs), circulating tumor cells, tumor-educated platelets, and cell-free nucleic acids. EVs are nanosize vesicles shuttling proteins, lipids, and nucleic acids, such as DNA, RNA, and non-coding RNAs (ncRNAs), that can induce phenotypic reprogramming of target cells. EVs are natural intercellular shuttles for ncRNAs, such as microRNAs (miRNAs) and circular-RNAs (circRNAs), known to have regulatory effects in OC. Here we focus on the involvement of circRNAs and miRNAs in OC cancer progression. The circRNA-microRNA-mRNA axis has been investigated with Circbank and miRwalk analysis, unraveling the intricate and detailed regulatory network created by EVs, ncRNAs, and mRNAs in OC.

Liquid Biopsy

The molecular landscape of the tumors has been typically established using the surgical or biopsy tissue samples resulting in a sampling bias offering only a single snapshot of tumor heterogeneity from the tissue-based tumor profiles. A rapid understanding of such a bias over the years has helped in procuring a precise portrait of the tumors. This practice has positioned the employability of currently employed molecular analysis of the circulating markers in blood and several other body fluids, such as urine, saliva, and pleural effusions, using liquid biopsies. The genomic profiling of the circulating markers such as circulating circulating tumor DNA (ctDNA), circulating tumor cells, or even RNA, proteins, and lipids as part of exosomes has not only guided the monitoring of response to treatment but also the drug resistance and minimal residual disease. The tumor educated platelets (TEPs) and their biological mechanisms driving the influencing of platelets by tumor cells are beginning to unearth TEPS as dynamically predominant components of liquid biopsy. Here, the biology, methodology, and clinical applications of liquid biopsy biomarkers are highlighted. The article puts forth how technological advances have catapulted cancer diagnosis via liquid biopsy in the last decade to obtain a tumor-derived genetic information for its exploitation toward personalized patient care so that liquid biopsy can come into routine clinical practice.

Abstract LB168: Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study

Abstract Background: Morpho-physiological alternations of platelets provided a rationale to harness RNA sequencing of tumor-educated platelets (TEPs) for preoperative diagnosis of cancer. Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Patients and Methods: This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n=3; Netherlands, n=5; Poland, n=1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. Results: The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. Analysis of public datasets suggested that TEPs had potential to detect multiple malignancies (Table 1). Conclusions: TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, early-stage ovarian cancer as well as other malignancies. However, these observations warrant prospective validations in a larger population before clinical utilities. Table 1. Performance for TEPs in public pan-cancer datasets. Disease n Healthy Control AUC, area under the curve (95% CI) Women NSCLC (non-small-cell lung cancer) 126 77 0.758 (0.691-0.825) Breast cancer 38 77 0.817 (0.726-0.909) Colorectal cancer 18 77 0.973 (0.945-1.000) Pancreatic cancer 16 77 0.993 (0.981-1.000) Glioblastoma 10 77 0.923 (0.831-1.000) Men NSCLC 119 82 0.746 (0.677-0.815) Colorectal cancer 25 82 0.933 (0.884-0.982) Pancreatic cancer 22 82 0.993 (0.984-1.000) Glioblastoma 19 82 0.981 (0.959-1.000) All NSCLC 245 159 0.774 (0.728-0.820) Colorectal cancer 40 159 0.978 (0.961-0.996) Breast cancer 38 159 0.821 (0.736-0.906) Pancreatic cancer 35 159 0.987 (0.974-0.999) Glioblastoma 35 159 0.931 (0.890-0.972) Hepatobiliary carcinomas 14 159 0.991 (0.978-1.000) Citation Format: Yue Gao, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G.j.g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, Guang-Yao Cai, Gui-Yan Xie, Shao-Qing Zeng, Yuan Wu, Jian-Hua Chi, Qiong Zhang, Xiao-Fei Jiao, Lin-Li Shi, Wan-Rong Lu, Wei-Guo Lv, Xing-Sheng Yang, Jurgen M.j. Piek, Cornelis D de Kroon, C.a.r. Lok, Anna Supernat, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Jacek Jassem, Bakhos A. Tannous, Nik Sol, Edward Post, Myron G. Best, Bei-Hua Kong, Xing Xie, Ding Ma, Thomas Wurdinger, An-Yuan Guo, Qing-Lei Gao. Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB168.

Molecular biomarkers and liquid biopsies in lung cancer

Liquid biopsy refers to the identification of tumor-derived materials in body fluids including in blood circulation. In the age of immunotherapy and targeted therapies used for the treatment of advanced malignancies, molecular analysis of the tumor is considered a crucial step to guide management. In lung cancer, the concept of liquid biopsies is particularly relevant given the invasiveness of tumor biopsies in certain locations, and the potential risks of biopsy in a patient population with significant co-morbidities. Liquid biopsies have many advantages including non-invasiveness, lower cost, potential for genomic testing, ability to monitor tumor evolution through treatment, and the ability to overcome spatial and temporal intertumoral heterogeneity. The potential clinical applications of liquid biopsy are vast and include screening, detection of minimal residual disease and/or early relapse after curative intent treatment, monitoring response to immunotherapy, and identifying mutations that might be targetable or can confer resistance. Herein, we review the potential role of circulating tumor DNA and circulating tumor cells as forms of liquid biopsies and blood biomarkers in non-small cell lung cancer. We discuss the methodologies/platforms available for each, clinical applications, and limitations/challenges in incorporation into clinical practice. We additionally review emerging forms of liquid biopsies including tumor educated platelets, circular RNA, and exosomes.

Multimodality in liquid biopsy: does a combination uncover insights undetectable in individual blood analytes?

Abstract The heterogeneity of each individual oncologic disease can be mirrored by molecular analysis of a simple blood draw in real time. Liquid biopsy testing has been shown useable for cancer detection, proof of minimal residual disease, therapy decision making and monitoring. However, an individual blood analyte does not present a comprehensive picture of the disease. It was recently shown that multi-modal/multi-parametric/multi-analyte liquid biopsy testing has the advantage of generating a high-resolution snapshot of the disease complexity. The different blood analytes such as circulating tumor cells, circulating immune cells, tumor-educated platelets, extracellular vesicles, cell-free DNA, cell-free RNA and circulating proteins complement each other and have additive value for clinical cancer management. We, here, like to review the studies leading to these promising conclusions and like to, at the end, mention that many challenges lie ahead before the translation into the clinic can be accomplished, including issues concerning clinical utility, method standardization, cost reimbursement and data management.

Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer.

Prostate cancer is the most dominant male malignancy worldwide. The clinical presentation of prostate cancer ranges from localized indolent to rapidly progressing lethal metastatic disease. Despite a decline in death rate over the past years, with the advent of early diagnosis and new treatment options, challenges remain towards the management of metastatic prostate cancer, particularly metastatic castration sensitive prostate cancer (mCSPC) and castration resistant prostate cancer (mCRPC). Current treatments involve a combination of chemotherapy with androgen deprivation therapy and/or androgen receptor signalling inhibitors. However, treatment outcomes are heterogeneous due to significant tumor heterogeneity indicating a need for better prognostic biomarkers to identify patients with poor outcomes. Liquid biopsy has opened a plethora of opportunities from early diagnosis to (personalized) therapeutic disease interventions. In this review, we first provide recent insights about (metastatic) prostate cancer and its current treatment landscape. We highlight recent studies involving various circulating biomarkers such as circulating tumor cells, genetic markers, circulating nucleic acids, extracellular vesicles, tumor-educated platelets, and the secretome from (circulating) tumor cells and tumor microenvironment in metastatic prostate cancer. The comprehensive array of biomarkers can provide a powerful approach to understanding the spectrum of prostate cancer disease and guide in developing improved and personalized treatments for patients.

RNA Sequencing of Tumor-Educated Platelets Reveals a Three-Gene Diagnostic Signature in Esophageal Squamous Cell Carcinoma.

There is no cost-effective, accurate, and non-invasive method for the detection of esophageal squamous cell carcinoma (ESCC) in clinical practice. We aimed to investigate the diagnostic potential of tumor-educated platelets in ESCC. In this study, seventy-one ESCC patients and eighty healthy individuals were enrolled and divided into a training cohort (23 patients and 27 healthy individuals) and a validation cohort (48 patients and 53 healthy individuals). Next-generation RNA sequencing was performed on platelets isolated from peripheral blood of all participants, and a support vector machine/leave-one-out cross validation (SVM/LOOCV) approach was used for binary classification. A diagnostic signature composed of ARID1A, GTF2H2, and PRKRIR discriminated ESCC patients from healthy individuals with 91.3% sensitivity and 85.2% specificity in the training cohort and 87.5% sensitivity and 81.1% specificity in the validation cohort. The AUC was 0.924 (95% CI, 0.845–0.956) and 0.893 (95% CI, 0.821–0.966), respectively, in the training cohort and validation cohort. This 3-gene platelet RNA signature could effectively discriminate ESCC from healthy control. Our data highlighted the potential of tumor-educated platelets for the noninvasive diagnosis of ESCC. Moreover, we found that keratin and collagen protein families and ECM-related pathways might be involved in tumor progression and metastasis of ESCC, which might provide insights to understand ESCC pathobiology and advance novel therapeutics.

Tumor-Educated Platelets as a Promising Biomarker for Blood-Based Detection of Renal Cell Carcinoma.

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.