Early detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle-derived long noncoding RNAs identified as markers.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim SS
PROVIDER: S-EPMC8486572 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Extracellular vesicles (EVs) are emerging as a new source of biomarkers in liquid biopsy because of their wide presence in most body fluids and their ability to load cargoes from disease-related cells. Owing to the crucial role of EVs in disease diagnosis and treatment, significant efforts have been made to isolate, detect, and analyze EVs with high efficiency. A recent overview of advanced EV detection nanotechnologies is discussed here. First, several key challenges in EV-based liquid biopsies are introduced. Then, the related pivotal advances in nanotechnologies for EV isolation based on physical features, chemical affinity, and the combination of nanostructures and chemical affinity are summarized. Next, a summary of high-sensitivity sensors for EV detection and advanced approaches for single EV detection are provided. Later, EV analysis is introduced in practical clinical scenarios, and the application of machine learning in this field is highlighted. Finally, future opportunities for the development of next-generation nanotechnologies for EV detection are presented.
| S-EPMC8529441 | biostudies-literature
Project description:Extracellular vesicles are cell-derived membranous vesicles that are secreted into biofluids. Emerging evidence suggests that EVs play an essential role in the pathogenesis of many diseases by transferring proteins, genetic material, and small signaling molecules between cells. Among these molecules, microRNAs (miRNAs), a type of small noncoding RNA, are one of the most important signals and are involved in various biological processes. Lung cancer is one of the leading causes of cancer-related deaths worldwide. Early diagnosis of lung cancer may help to reduce mortality and increase the 5 years survival rate and thereby reduce the associated socioeconomic burden. In the past, EV-miRNAs have been recognized as biomarkers of several cancers to assist in diagnosis or prognosis. In this review, we discuss recent findings and clinical practice for EV-miRNAs of lung cancer in several biofluids, including blood, bronchoalveolar lavage fluid (BALF), and pleural lavage.
| S-EPMC7943919 | biostudies-literature
Project description:Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker-detected via a liquid biopsy-for the noninvasive diagnosis of lung cancer.
| S-EPMC8067192 | biostudies-literature
Project description:Rationale: Long extracellular RNAs (exRNAs) in plasma can be profiled by new sequencing technologies, even with low abundance. However, cancer-related exRNAs and their variations remain understudied. Methods: We investigated different variations (i.e. differential expression, alternative splicing, alternative polyadenylation, and differential editing) in diverse long exRNA species (e.g. long noncoding RNAs and circular RNAs) using 79 plasma exosomal RNA-seq (exoRNA-seq) datasets of multiple cancer types. We then integrated 53 exoRNA-seq datasets and 65 self-profiled cell-free RNA-seq (cfRNA-seq) datasets to identify recurrent variations in liver cancer patients. We further combined TCGA tissue RNA-seq datasets and validated biomarker candidates by RT-qPCR in an individual cohort of more than 100 plasma samples. Finally, we used machine learning models to identify a signature of 3 noncoding RNAs for the detection of liver cancer. Results: We found that different types of RNA variations identified from exoRNA-seq data were enriched in pathways related to tumorigenesis and metastasis, immune, and metabolism, suggesting that cancer signals can be detected from long exRNAs. Subsequently, we identified more than 100 recurrent variations in plasma from liver cancer patients by integrating exoRNA-seq and cfRNA-seq datasets. From these datasets, 5 significantly up-regulated long exRNAs were confirmed by TCGA data and validated by RT-qPCR in an independent cohort. When using machine learning models to combine two of these validated circular and structured RNAs (SNORD3B-1, circ-0080695) with a miRNA (miR-122) as a panel to classify liver cancer patients from healthy donors, the average AUROC of the cross-validation was 89.4%. The selected 3-RNA panel successfully detected 79.2% AFP-negative samples and 77.1% early-stage liver cancer samples in the testing and validation sets. Conclusions: Our study revealed that different types of RNA variations related to cancer can be detected in plasma and identified a 3-RNA detection panel for liver cancer, especially for AFP-negative and early-stage patients.
| S-EPMC7681086 | biostudies-literature
Project description:The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.
| S-EPMC6721601 | biostudies-literature
Project description:Disseminated disease is present in ?50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.
| S-EPMC7055306 | biostudies-literature
Project description:A diverse pool of RNAs remain encapsulated within the transcriptionally silent spermatozoon despite the dramatic reduction in cellular and nuclear volume following cytoplasm/nucleoplasm expulsion. The impact of this pronounced restructuring on the distribution of transcripts inside the sperm essentially remains unknown. To define their compartmentalization, total RNA >100 nt was extracted from sonicated (SS) mouse spermatozoa and detergent demembranated sucrose gradient fractionated (Cs/Tx) sperm heads. Sperm RNAs predominately localized toward the periphery. The corresponding distribution of transcripts and thus localization and complexity were then inferred by RNA-seq. Interestingly, the number of annotated RNAs in the CsTx sperm heads exhibiting reduced peripheral enrichment was restricted. However this included Cabyr, the calcium-binding tyrosine phosphorylation-regulated protein encoded transcript. It is present in murine zygotes prior to the maternal to the zygotic transition yet absent in oocytes, consistent with the delivery of internally positioned sperm-borne RNAs to the embryo. In comparison, transcripts enriched in sonicated sperm contributed to the mitochondria and exosomes along with several nuclear transcripts including the metastasis associated lung adenocarcinoma transcript 1 (Malat1) and several small nucleolar RNAs. Their preferential peripheral localization suggests that chromatin remodeling during spermiogenesis is not limited to nucleoproteins as part of the nucleoprotein exchange.
| S-EPMC4538811 | biostudies-literature
Project description:Previously, abnormal extracellular vesicle (EV) sorting of miR-193a was identified in colorectal cancer (CRC) progression. Although a reduced level of miR-193a-5p in plasma/serum has been reported in many different types of cancer, the EV-derived miR-193a-5p level in CRC and its potential application as a minimally invasive biomarker are still unknown. Here, we evaluated the circulating EV-derived miR-193a-5p expression levels in a cohort of 101 participants by real-time quantitative polymerase chain reaction (RT-qPCR). We found that plasma EV-miR-193a-5p decreased significantly in CRC patients as compared with precancerous colorectal adenoma (CA) and non-cancerous control (NC) individuals. The circulating EV-miR-193a-5p showed an area under the receiver operating characteristic curve (AUC) of 0.740 in distinguishing CRC from CA and an AUC of 0.759 in distinguishing CRC from NC. Furthermore, the suppression on CRC cells of miR-193a-5p was verified by transwell, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), EdU, RT-qPCR, and western blotting. Bioinformatic analysis predicted 32 genes, which were the most likely miR-193a-5p targeted and mainly focused on tumor progression. Among them, we revealed that miR-193a-5p could inhibit CRC migration and invasion via targeting tumor-associated genes like CUT-like homeobox 1 (CUX1) and intersectin 1 (ITSN1). In conclusion, miR-193a-5p could suppress CRC development, and decreased plasma EV-miR-193a-5p could be a promising biomarker for human CRC detection.
| S-EPMC7461920 | biostudies-literature
Project description:Bone metastases is one of the common metastatic site and leading cause of cancer-related mortality in progressive cancer patients. The purpose of the present study is to establish a liquid biopsy based multi-gene classifier and associated signalling pathways for early diagnosis of bone metastases. We used publically available microarray datasets and analysed them in a platform/chip-specific manner using GeneSpring software. Analyses of gene expression datasets identified 15 consistently over-expressed genes with statistical significance. Further, expression profile of same set of 15 genes were compared in breast and lung cancer exosome derived mRNA with (n = 10) and without (n = 10) bone metastases against healthy controls. ROC curve analysis performed individually for all the 15 genes shortlisted the 5 most relevant genes with significant sensitivity and specificity in both cancers. This liquid biopsy-based bone metastases predictor using multi-gene panel is a unique approach with potential clinical applications for effective management of aggressive cancers.
| S-EPMC8220227 | biostudies-literature
Project description:Cardiovascular disorders such as heart failure are leading causes of mortality. Patient stratification via identification of novel biomarkers could improve management of cardiovascular diseases of complex etiologies. Long-noncoding RNAs (lncRNAs) are highly tissue-specific in nature and have emerged as important biomarkers in human diseases. In this study, we aimed to identify cardiac-enriched lncRNAs as potential biomarkers for cardiovascular conditions. Deep RNA sequencing and quantitative PCR identified differentially expressed lncRNAs between failing and non-failing hearts. An independent dataset was used to evaluate the enrichment of lncRNAs in normal hearts. We identified a panel of 2906 lncRNAs, named FIMICS, that were either cardiac-enriched or differentially expressed between failing and non-failing hearts. Expression of lncRNAs in blood samples differentiated patients with myocarditis and acute myocardial infarction. We hereby present the FIMICS panel, a readily available tool to provide insights into cardiovascular pathologies and which could be helpful for diagnosis, monitoring and prognosis purposes.
| S-EPMC9898641 | biostudies-literature