Simultaneous Detection of Tumor Derived Exosomal Protein–MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis

Hsu, Chang-Chieh; Yang, Yunchen; Kannisto, Eric; Zeng, Xie; Yu, Guan; Patnaik, Santosh K.; Dy, Grace K.; Reid, Mary E.; Gan, Qiaoqiang; Wu, Yun

doi:10.1021/acsnano.2c10970

Cited by 35 publications

(12 citation statements)

References 85 publications

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“…We summarized the analytical performance of our developed system by comparing recently published EV‐miRNA detection methods (Table S3 , Supporting Information). [ 29 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] The new approach now enables quantifying EVs containing target RNA, and this new capability could be readily extended to multiplexed EV protein and RNA analysis at a single EV level.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas13a‐Based MicroRNA Detection in Tumor‐Derived Extracellular Vesicles

et al. 2023

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MicroRNAs (miRNAs) in extracellular vesicles (EVs) play essential roles in cancer initiation and progression. Quantitative measurements of EV miRNAs are critical for cancer diagnosis and longitudinal monitoring. Traditional PCR‐based methods, however, require multi‐step procedures and remain as bulk analysis. Here, the authors introduce an amplification‐free and extraction‐free EV miRNA detection method using a CRISPR/Cas13a sensing system. CRISPR/Cas13a sensing components are encapsulated in liposomes and delivered them into EVs through liposome‐EV fusion. This allows for accurately quantify specific miRNA‐positive EV counts using 1 × 108 EVs. The authors show that miR‐21‐5p‐positive EV counts are in the range of 2%–10% in ovarian cancer EVs, which is significantly higher than the positive EV counts from the benign cells (<0.65%). The result show an excellent correlation between bulk analysis with the gold‐standard method, RT‐qPCR. The authors also demonstrate multiplexed protein‐miRNA analysis in tumor‐derived EVs by capturing EpCAM‐positive EVs and quantifying miR‐21‐5p‐positive ones in the subpopulation, which show significantly higher counts in the plasma of cancer patients than healthy controls. The developed EV miRNA sensing system provides the specific miRNA detection method in intact EVs without RNA extraction and opens up the possibility of multiplexed single EV analysis for protein and RNA markers.

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Section: Discussionmentioning

confidence: 99%

CRISPR/Cas13a‐Based MicroRNA Detection in Tumor‐Derived Extracellular Vesicles

et al. 2023

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“…In the past two decades, EVs and miRNA in liquid biopsies have been intensively explored for their potential in the early detection of liver and other cancers [ 37 , 38 , 39 ]. Here, we addressed the question as to whether EVs isolated from the conditioned media of hepatoma cell lines contain miRNAs responsible for liver cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts

Petővári,

Tóth,

Turiák

et al. 2023

IJMS

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Tumors are intricate ecosystems where cancer cells and non-malignant stromal cells, including cancer-associated fibroblasts (CAFs), engage in complex communication. In this study, we investigated the interaction between poorly (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts. We explored various communication channels, including soluble factors, metabolites, extracellular vesicles (EVs), and miRNAs. Co-culture with HLE cells induced LX2 to produce higher levels of laminin β1, type IV collagen, and CD44, with pronounced syndecan-1 shedding. Conversely, in HuH7/LX2 co-culture, fibronectin, thrombospondin-1, type IV collagen, and cell surface syndecan-1 were dominant matrix components. Integrins α6β4 and α6β1 were upregulated in HLE, while α5β1 and αVβ1 were increased in HuH7. HLE-stimulated LX2 produced excess MMP-2 and 9, whereas HuH7-stimulated LX2 produced excess MMP-1. LX2 activated MAPK and Wnt signaling in hepatoma cells, and conversely, hepatoma-derived EVs upregulated MAPK and Wnt in LX2 cells. LX2-derived EVs induced over tenfold upregulation of SPOCK1/testican-1 in hepatoma EV cargo. We also identified liver cancer-specific miRNAs in hepatoma EVs, with potential implications for early diagnosis. In summary, our study reveals tumor type-dependent communication between hepatoma cells and fibroblasts, shedding light on potential implications for tumor progression. However, the clinical relevance of liver cancer-specific miRNAs requires further investigation.

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“…Tumor heterogeneity, such as intratumoral heterogeneity and synchronous multifocal tumors with different clones, poses significant challenges for closely monitoring the tumor’s progression and subsequent treatment. , It is commonly manifested by distinct expression levels of specific biomolecules (transcriptome level or proteome level) located in the cytoplasm or cytomembrane, which act as important biomarkers in cancer diagnosis and prognosis . As one of the most widely studied noncoding RNA, micro-RNAs (miRNAs) in cytoplasm dynamically regulate the physiological activities of cancer cells and are closely related to the migration and invasion of various cancers . miRNAs are reported to exist with considerable intratumoral heterogeneity within primary breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Zipper-Confined DNA Nanoframe for High-Efficient and High-Contrast Imaging of Heterogeneous Tumor Cell

Zhang,

Yang,

et al. 2024

Anal. Chem.

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Current study in the heterogeneity and physiological behavior of tumor cells is limited by the fluorescence in situ hybridization technology in terms of probe assembly efficiency, background suppression capability, and target compatibility. In a typically well-designed assay, hybridization probes are constructed in a confined nanostructure to achieve a rapid assembly for efficient signal response, while the excessively high local concentration between different probes inevitably leads to nonspecific background leakage. Inspired by the fabric zipper, we propose a novel confinement reaction pattern in a zipper-confined DNA nanoframe (ZCDN), where two kinds of hairpin probes are independently anchored respective tracks. The metastable states of the dual tracks can well avoid signal leakage caused by the nonspecific probe configuration change. Biomarkermediated proximity ligation reduces the local distance of dual tracks, kinetically triggering an efficient allosteric chain reaction between the hairpin probes. This method circumvents nonspecific background leakage while maintaining a high efficiency in responding to targets. ZCDN is employed to track different cancer biomarkers located in both the cytoplasm and cytomembrane, of which the expression level and oligomerization behavior can provide crucial information regarding intratumoral heterogeneity. ZCDN exhibits high target response efficiency and strong background suppression capabilities and is compatible with various types of biological targets, thus providing a desirable tool for advanced molecular diagnostics.

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Simultaneous Detection of Tumor Derived Exosomal Protein–MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis

Cited by 35 publications

References 85 publications

CRISPR/Cas13a‐Based MicroRNA Detection in Tumor‐Derived Extracellular Vesicles

CRISPR/Cas13a‐Based MicroRNA Detection in Tumor‐Derived Extracellular Vesicles

Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts

Zipper-Confined DNA Nanoframe for High-Efficient and High-Contrast Imaging of Heterogeneous Tumor Cell

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