A Non-invasive Liquid Biopsy Screening of Urine-Derived Exosomes for miRNAs as Biomarkers in Endometrial Cancer Patients

Srivastava, Akhil; Moxley, Katherine M.; Ruskin, R.; Dhanasekaran, Danny N.; Zhao, Yan; Ramesh, Rajagopal

doi:10.1208/s12248-018-0220-y

Cited by 82 publications

(69 citation statements)

References 52 publications

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“…Additionally, EVs are relatively stable over time and include proteins and nucleic acids from their parental tumors 66 . Thus, cancer patient plasma could serve as a reference for in vivo tumors 67,68 .…”

Section: Resultsmentioning

confidence: 99%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Zhong

2019

Sci Rep

174

137

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For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the “gold standard”. 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D- culture derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D- culture derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D- culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D- culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

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Section: Resultsmentioning

confidence: 99%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Zhong

2019

Sci Rep

174

137

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“…Likewise, by evaluating the expression profile of miRNAs in endometrial cancer (EC) and urine-derived exosomes from suspected patients, it was found that differentially expressed miRNAs can be used as biomarkers for EC diagnosis. 38 Tumor cells can secrete a large number of exosomes, and the specific antigens on their surface can reflect the nature of donor cells. Therefore, tumor exosomes have attracted great attention in cancer research.…”

Section: Classificationmentioning

confidence: 99%

<p>Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications</p>

Zhang¹,

Bi²,

Huang³

et al. 2020

IJN

711

624

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Exosomes are nano-sized small extracellular vesicles secreted by cells, carrying nucleic acids, proteins, lipids and other bioactive substances to play a role in the body's physiological and pathological processes. Compared to synthetic carriers such as liposomes and nanoparticles, the endogeneity and heterogeneity of exosomes give them extensive and unique advantages in the field of disease diagnosis and treatment. However, the storage stability, low yield, low purity, and weak targeting of exosomes limit its clinical application. For this reason, further exploration is needed to optimize the above problems and facilitate future functional studies of exosomes. In this paper, the origin, classification, preparation and characterization, storage stability and applications of exosome delivery system are summarized and discussed by searching a large number of literatures.

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“…Angiogenesis has been shown to play an important role in the growth of EC (85) while PDCD4 expression has been linked to tumor grade in endometrioid EC (86). Srivastava and colleagues studied 81 microRNAs from urine derived exosomes from patients with and without EC, 57 of which were amplified in qPCR and reported has-miR-200c-3p to be differentially expressed (60). miR-200c is a tumor suppressor microRNA that prevents the epithelial to mesenchymal transition of cancer cells and has been found to be dysregulated in many cancers (87).…”

Section: Urinary Cell-free and Extracellular Vesicle Micrornasmentioning

confidence: 99%

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

et al. 2020

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Endometrial cancer is the most common malignancy of the female genital tract and its incidence is rising in parallel with the mounting prevalence of obesity. Early diagnosis has great potential to improve outcomes as treatment can be curative, especially for early stage disease. Current tests and procedures for diagnosis are limited by insufficient accuracy in some and unacceptable levels of invasiveness and discomfort in others. There has, therefore, been a growing interest in the search for sensitive and specific biomarkers for endometrial cancer detection based on non-invasive sampling methodologies. Urine, the prototype non-invasive sample, is attractive for biomarker discovery as it is easily accessible and can be collected repeatedly and in quantity. Identification of urinary biomarkers for endometrial cancer detection relies on the excretion of systemic biomarkers by the kidneys or urinary contamination by biomarkers shed from the uterus. In this review, we present the current standing of the search for endometrial cancer urinary biomarkers based on cytology, genomic, transcriptomic, proteomic, and metabolomic platforms. We summarize the biomarker candidates and highlight the challenges inherent in urinary biomarker discovery. We review the various technologies with promise for biomarker detection and assess these novel approaches for endometrial cancer biomarker research.

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A Non-invasive Liquid Biopsy Screening of Urine-Derived Exosomes for miRNAs as Biomarkers in Endometrial Cancer Patients

Cited by 82 publications

References 52 publications

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

<p>Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications</p>

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

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