Gastric cancer (GC) is among the most common malignant tumors and remains a leading cause of cancer-related mortality worldwide. Furthermore, exosomal miRNAs are regarded as promising noninvasive biomarkers for diagnosing malignant tumors.

To investigate the expression of exosomal miR-17-92 clusters and develop a potential biomarker for GC diagnosis

Exosomes were isolated from serum samples obtained from 72 GC patients and 20 healthy controls. The isolated exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Exosomal RNA was then extracted, and the expression profile of the miR-17-92 cluster was analyzed using qRT-PCR. Statistical methods were employed to evaluate the relationship between the serum exosomal miR-17-92 cluster expression and the clinicopathological parameters of GC patients as well as to assess the diagnostic utility of these miRNAs.

The expression of four members of the exosomal miR-17-92 cluster-miR-17, miR-18, miR-19a, and miR-92-was significantly upregulated in the serum samples of patients with GC compared with those of healthy controls. The miR-17-92 cluster panel demonstrated substantially higher clinical diagnostic value for GC than any individual component or pair. Additionally, the expression of traditional tumor biomarkers-carcinoembryonic antigen and carbohydrate antigen 19-9-was significantly elevated in the serum of patients with GC compared with that of healthy controls. Each biomarker, whether alone or in combination, effectively differentiated the patients from healthy controls. Furthermore, a combined panel of the two traditional tumor biomarkers and the four miR-17-92 cluster members exhibited the highest diagnostic accuracy for GC. Elevated miR-17-92 expression was also strongly associated with tumor size, tumor depth, lymph node metastasis, distant metastasis, and tumor-node-metastasis stage.

Our findings revealed that the circulating exosomal miR-17-92 cluster may be used as a potential noninvasive biomarker to improve diagnostic efficiency for GC.

• Gastric cancer
• Serum
• Exosome
• miR-17-92 cluster
• Diagnosis

• bioinformatics
• cancer
• data analysis

• Stomach Neoplasms/genetics
• Stomach Neoplasms/immunology
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Immunity/genetics

• 202202024 Science and Technology Planning Project for Health of Inner Mongolia
• 2022QN06007 Natural Science Foundation of Inner Mongolia Autonomous Region
• 2021YN18 Science Research Foundation of Inner Mongolia People's Hospital
• 62171241 National Natural Science Foundation of China
• 62262049 National Natural Science Foundation of China
• 81960449 National Natural Science Foundation of China
• Natural Science Foundation of Inner Mongolia Autonomous Region
• National Natural Science Foundation of China

• cancer progression
• diagnosis markers
• exosomes
• survival

• EVs
• early diagnosis
• exosomes
• gastric cancer
• gastric juice
• liquid biopsy
• miRNA

• Humans
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/genetics
• MicroRNAs/metabolism
• MicroRNAs/genetics
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Liquid Biopsy/methods

• cancer
• diagnosis
• exosome
• therapy
• translational research

• Melanoma
• biomarker
• exosomes
• lipid-bilayer.
• non-coding RNAs
• therapeutic targets

• Humans
• Melanoma/diagnosis
• Melanoma/drug therapy
• Melanoma/metabolism
• Melanoma/genetics
• Melanoma/pathology
• Melanoma/therapy
• Exosomes/metabolism
• Exosomes/genetics
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism

• EVtrap
• bladder cancer
• extracellular vesicles
• proteomics
• urine

• Humans
• Proteome/analysis
• Proteomics/methods
• Biomarkers/metabolism
• Mass Spectrometry
• Extracellular Vesicles/chemistry

• P30 CA023168 NCI NIH HHS
• R44 CA239845 NCI NIH HHS
• RF1 AG064250 NIA NIH HHS

• biomarker
• exosomes
• gastrointestinal cancers
• liquid biopsy

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.

The pre-metastatic niche is a recently established concept that could lead to targeted therapies that prevent metastasis before ever occurring. Considering that 90% of cancer mortality results from metastasis, the PMN is thus a salient opportunity for intervention. The purpose of the current review is to cover what is known specifically about the hepatic pre-metastatic niche, a topic that has garnered increasing research focus within the last decade. We discuss the methods of communication between primary tumors and the liver, the involved cell populations, the key changes within liver tissue, and perspectives on the future of the field.

Primary tumors can communicate with the liver to establish a microenvironment that favors metastatic colonization prior to dissemination, forming what is termed the “pre-metastatic niche” (PMN). Through diverse signaling mechanisms, distant malignancies can both influence hepatic cells directly as well as recruit immune cells into the PMN. The result is a set of changes within the hepatic tissue that increase susceptibility of tumor cell invasion and outgrowth upon dissemination. Thus, the PMN offers a novel step in the traditional metastatic cascade that could offer opportunities for clinical intervention. The involved signaling molecules also offer promise as biomarkers. Ultimately, while the existence of the hepatic PMN is well-established, continued research effort and use of innovative models are required to reach a functional knowledge of PMN mechanisms that can be further targeted.

Gastric cancer (GC) is one of the most common cancers and the fifth leading cause of cancer-related deaths worldwide. The steadily growing interest in secreted extracellular vesicles (EVs) is related to their ability to carry a variety of biologically active molecules, which can be used as markers for liquid noninvasive diagnosis of malignant neoplasms. For these applications, blood is the most widely used source of EVs. However, this body fluid contains an extremely heterogeneous mixture of EVs originating from different types of normal cells and tissues. The aim of this study was to assess the possibility of using gastric juice (GJ) as an alternative source of EVs since it is expected to be enriched in vesicles of tumor origin. We validated the presence of EVs in GJ using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western-blot analysis of exosomal markers, showed for the first time the feasibility of their isolation by ultracentrifugation and demonstrated the prospect of using GJ-derived EVs as a source of GC miRNA markers.

EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.

• Biomarkers, Tumor/metabolism
• Cell Communication
• Extracellular Vesicles/metabolism
• Humans
• Liquid Biopsy
• Signal Transduction
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Tumor Microenvironment

• National Key Research and Development Program of China
• National Natural Science Foundation of China

• detection methods
• exosomes
• molecular biomarkers
• tumor-derived exosomes

• Biomarkers, Tumor
• Cell-Free Nucleic Acids
• Circulating Tumor DNA
• Disease Susceptibility
• Early Detection of Cancer/methods
• Exosomes/metabolism
• Humans
• Liquid Biopsy/methods
• Molecular Diagnostic Techniques
• Neoplasms/diagnosis
• Neoplasms/etiology
• Neoplasms/metabolism
• Oncogene Proteins
• SELEX Aptamer Technique
• Spectrum Analysis, Raman/methods

• LY20H160008 Zhejiang Provincial Natural Science Foundation of China
• LHDMZ22H300001 Joint Funds of the Zhejiang Provincial Natural Science Foundation of China
• 82074052 National Natural Science Foundation of China
• 2022ZZ024 Key Research Project of Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program
• 81730108 Key projects of National Natural Science Foundation of China

• biomarkers
• body fluids
• exosomes
• hallmarks
• miRNAs

Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, differentiation, and apoptosis. miR-23b have been identified to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inflammation resistance to various autoimmune diseases and restrained inflammatory cell migration. The characterization of the specific alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR-23b and its target genes in different models and offer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inflammatory cell activation, differentiation, and migration.

• circRNAs
• exosomes
• function
• gastric cancer

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation.

• exosomes (EX)
• extracellular environment
• metastase
• pre-metastastic niche
• tumor

Exosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.

• Biomarker
• Exosome
• Gastric cancer
• Progression
• ncRNA

• Biomarker
• exosomes
• extracellular vesicles
• gastrointestinal cancers
• inflammatory bowel disease
• liquid biopsy

The screening methods and therapeutic strategies for gastrointestinal cancer (GIC) have improved, but mortality in GIC patients remains high. Early detection and precise evaluation of GIC are required to further improve treatment outcomes in GIC patients. MicroRNAs (miRNAs), which do not encode proteins, have attracted attention as biomarkers of various diseases. Since the first report revealing the strong correlation between miRNAs and cancer in 2002, numerous studies have illustrated the changes in the expression and the biological and oncological effects of miRNAs in GIC. Furthermore, miRNAs circulating in the blood are reported to be associated with GIC status. These miRNAs are thought to be useful as noninvasive biomarkers because of their stability in blood. Herein, we discuss the potential of miRNAs as noninvasive biomarkers for each type of GIC on the basis of previous reports and describe perspectives for their future application.

Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers.

• circulating microRNA
• gastrointestinal cancer
• noninvasive tumor markers

• biomarker
• cancer therapy
• exosomes
• gastric cancer
• molecular mechanism
• non-coding RNAs

To improve clinical outcomes, early diagnosis is mandatory in cancer patients. Several diagnostic approaches have been proposed, however, the main drawback relies on the invasive procedures required. Extracellular vesicles (EVs) are bilayer lipid membrane structures released by almost all cells and transferred to remote sites via the bloodstream. The observation that their cargo reflects the cell of origin has opened a new frontier for non-invasive biomarker discovery in oncology. Moreover, since EVs can be recovered from different body fluids, their impact as a Correctdiagnostic tool has gained particular interest. Hence, in the last decade, several studies using different biological fluids have been performed, showing the valuable contributions of EVs as tumour biomarkers, and their improved diagnostic power when combined with currently available tumour markers. In this review, the most relevant data on the diagnostic relevance of EVs, alone or in combination with the well-established tumour markers, are discussed.

Early diagnosis, along with innovative treatment options, are crucial to increase the overall survival of cancer patients. In the last decade, extracellular vesicles (EVs) have gained great interest in biomarker discovery. EVs are bilayer lipid membrane limited structures, released by almost all cell types, including cancer cells. The EV cargo, which consists of RNAs, proteins, DNA, and lipids, directly mirrors the cells of origin. EVs can be recovered from several body fluids, including blood, cerebral spinal fluid (CSF), saliva, and Broncho-Alveolar Lavage Fluid (BALF), by non-invasive or minimally invasive approaches, and are therefore proposed as feasible cancer diagnostic tools. In this review, methodologies for EV isolation and characterization and their impact as diagnostics for the central nervous system, head and neck, lung, and gastrointestinal cancers are outlined. For each of these tumours, recent data on the potential clinical applications of the EV’s unique cargo, alone or in combination with currently available tumour biomarkers, have been deeply discussed.

• cancer
• cancer diagnostic biomarkers
• extracellular vesicles
• liquid biopsy

• Diagnosis
• Exosomes
• Gastric cancer
• Molecular mechanism
• Small extracellular vesicles
• Therapy

• Congressionally Directed Medical Research Programs
• Natural Sciences and Engineering Research Council of Canada

Gastric cancer (GC) is one of the most common malignancies in the world. Exosomes, a subset of extracellular vesicles with an average diameter of 100 nm, contain and transfer a variety of functional macromolecules such as proteins, lipids, and nucleic acids. A large number of studies indicated that exosomes can play a significant role in the initiation and development of GC via facilitating intercellular communication between gastric cancer cells and microenvironment. Exosomal RNAs, one of the key functional cargos, are involved in the pathogenesis, development, and metastasis of GC. In addition, recent studies elucidated that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for GC. In this review, we summarized the function of exosomal RNA in the tumorigenesis, progression, diagnosis, and treatment of GC, which may further unveil the functions of exosome and promote the potentially diagnostic and therapeutic application of exosomes in GC.

• biomarker
• exosomal RNAs
• exosome
• gastric cancer

• HCC
• biomarker
• drug resistance
• ectosomes
• exosomes
• extracellular vesicles
• gastrointestinal and liver cancers
• microvesicles

• 410853455 Deutsche Forschungsgemeinschaft

• early diagnosis
• exosomes
• gastric cancer
• liquid biopsy
• microRNAs

Exosomes are essential for tumor growth, metastasis, and are used as novel signaling molecules in targeted therapies. Therefore, exosomal miRNAs can be used in new diagnostic and therapeutic approaches due to their involvement in the development of cancers. However, the detailed biological function, potential molecular mechanism and clinical application of exo-miR-15b-3p in gastric cancer (GC) remains unclear.

miR-15b-3p mRNA levels in tissues, serum, cells and exosomes were analyzed using qRT-PCR assays. qRT-PCR, immunohistochemical and western blotting analyses were utilized for the determination of DYNLT1 expression. The interrelationship connecting miR-15b-3p with DYNLT1 was verified using Dual-luciferase report, western blotting and qRT-PCR assays. Fluorescent PKH-26 or GFP-Lv-CD63 labeled exosomes, as well as Cy3-miR-15b-3p, were utilized to determine the efficacy of the transfer of exo-miR-15b-3p between BGC-823 and recipient cells. Several in vitro assays and xenograft tumor models were conducted to determine exo-miR-15b-3p impact on GC progression.

This is the first study to confirm high miR-15b-3p expression in GC cell lines, tissues and serum. Exosomes obtained from 108 GC patient serum samples and GC cell-conditioned medium were found to show upregulation of exo-miR-15b-3p, with the area under the ROC curve (AUC) being 0.820 [0.763–0.876], which is superior to the AUC of tissues and serum miR-15b-3p (0.674 [0.600–0.748] and 0.642 [0.499–0.786], respectively). In addition, high exo-miR-15b-3p expression in serum was found to accurately predict worse overall survival. SGC-7901 and GES-1 cells are capable of internalizing BGC-823 cell-derived exosomes, allowing the transfer of miR-15b-3p. Migration, invasion, proliferation and inhibition of apoptosis in vitro and in vivo were enhanced by exo-miR-15b-3p, by restraining DYNLT1, Cleaved Caspase-9 and Caspase-3 expression.

This study identified a previously unknown regulatory pathway, exo-miR-15b-3p/DYNLT1/Caspase-3/Caspase-9, which promotes GC development and GES-1 cell malignant transformation. Therefore, serum exo-miR-15b-3p may be a potential GC diagnosis and prognosis biomarker, which can be used in precise targeted GC therapy.

• Apoptosis
• Cleaved Caspase-3
• Cleaved Caspase-9
• DYNLT1
• Exosomes
• Gastric cancer
• miR-15b-3p

• Biomarkers
• Colorectal cancer
• Esophageal cancer
• Gastric cancer
• Gastrointestinal cancer
• Gene panel
• Liquid biopsy
• Precision medicine
• Precision surgery

• CEBPA-AS1
• diagnosis
• exosome
• gastric cancer
• lncRNAs

As the majority of cancers and gestational diseases are prognostically stage- and grade-dependent, the ultimate goal of ongoing studies in precision medicine is to provide early and timely diagnosis of such disorders. These studies have enabled the development of various new diagnostic biomarkers, such as free circulating nucleic acids, and detection of their epigenetic changes. Recently, extracellular vesicles including exosomes, microvesicles, oncosomes, and apoptotic bodies have been recognized as powerful diagnostic tools. Extracellular vesicles carry specific proteins, lipids, DNAs, mRNAs, and miRNAs of the cells that produced them, thus reflecting the function of these cells. It is believed that exosomes, in particular, may be the optimal biomarkers of pathological pregnancies and cancers, especially those that are frequently diagnosed at an advanced stage, such as ovarian cancer. In the present review, we survey and critically appraise novel epigenetic biomarkers related to free circulating nucleic acids and extracellular vesicles, focusing especially on their status in trophoblasts (pregnancy) and neoplastic cells (cancers).

• cell-free DNA
• cell-free fetal DNA
• cell-free tumor DNA
• exosomes
• extracellular vesicles
• microRNA

• exosome
• gastric cancer
• liquid biomarker
• miRNA-21
• miRNA-92a
• peritoneal recurrence
• prognosis

• Biomarker
• Chemoresistance
• Exosome-dependent drug delivery
• Long non-coding RNA
• MiRNA
• Signaling pathways

• Body Fluids/metabolism
• Carcinogenesis/genetics
• Carcinogenesis/pathology
• Drug Delivery Systems
• Exosomes/genetics
• Exosomes/physiology
• Humans
• MicroRNAs/genetics
• Neoplasm Metastasis/genetics
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Tumor Microenvironment/physiology

• Drug resistance
• Exosomes
• Extracellular vesicles
• Gastric cancer
• Tumor microenvironment

Exosomes are nanosized extracellular vesicles that can be released by almost all types of cells. Initially considered as the garbage bins acting to discard unwanted products of cells, exosomes are now recognized as an important way for cellular communication by transmitting bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. The recent studies have shown that exosomes are critically involved in human health and diseases including cancer. Exosomes have been suggested to participate in the promotion of tumorigenesis, tumor growth and metastasis, tumor angiogenesis, tumor immune escape, and tumor therapy resistance. Increasing evidence indicate that exosomes play important roles in gastric cancer development and progression. In this review, we summarized the current understanding of exosomes in gastric cancer with an emphasis on the biological roles of exosomes in gastric cancer and their potential as biomarkers for gastric cancer diagnosis as well as potential targets for gastric cancer therapy.

• Biomarker
• Exosomes
• Gastric cancer
• Progression
• Target

Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.

To summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.

Relevant publications in the literature were identified by search of the “PubMed” database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers, 47 biomarkers and 2240 patients from 30 studies were included.

Our results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.

Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.

• Exosome
• Biomarker
• Cancer
• Diagnosis
• Prognosis