Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA390771 | ENA |
REPOSITORIES: ENA
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Project description:Endogenous and exogenous extracellular RNAs will be characterized in four body fluids (plasma, serum, CSF and saliva) collected at the same time from 134 healthy subjects ranging in age from 31 to 101 years old. Small RNAs contained in these samples will be profiled by small RNA-seq using unfractionated biofluids and purified extracellular vesicles.
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Project description:Endogenous and exogenous extracellular RNAs will be characterized in four body fluids (plasma, serum, CSF and saliva) collected at the same time from 134 healthy subjects ranging in age from 31 to 101 years old. Small RNAs contained in these samples will be profiled by small RNA-seq using unfractionated biofluids and purified extracellular vesicles.
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Project description:Numerous studies have demonstrated that microRNAs (miRNAs) are stably detectable in blood and can serve as useful biomarkers for cancer. Here, using 29 cell lines representing 6 tumor types, 2 biocollections, and one large dataset of non-small cell lung cancer (NSCLC) patients and healthy subjects, we set an in vitro - ex vivo strategy to detect miRNAs that could be used as circulating biomarker for cancers. We thus found that hsa-miR-614 was highly enriched in the small extracellular vesicles (EVs) released by NSCLC cancer cell lines, and that serum expression of hsa-miR-614 alone produced a receiver-operating characteristic (ROC) curve area (AUC) of 0.953, with high sensitivity and specificity for distinguishing NSCLC patients from healthy controls. Altogether, our data support the notion that circulating miRNAs were readily detectable in pre-clinical cell line models as well as in blood, where they appeared to distinguish patients and healthy subjects.
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Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
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Project description:Small extracellular vesicles (sEV) are nano-sized (40-150 nm), membrane-encapsulated vesicles that are released by malignant or pathologic and non-pathologic cells into the extracellular space and function as intercellular signaling vectors through the horizontal transfer of biologic molecules, including microRNA (miRNA) and other small non-coding RNA (ncRNA), that can alter the phenotype of recipient cells. sEV are present in essentially all extracellular biofluids, including serum, urine and saliva, and offer a new avenue for discovery and development of novel biomarkers of various disease states and exposures. The objective of this study was to determine the similarities and differences between sEV ncRNA derived from saliva, serum and urine, as well as cell-free ncRNA from serum. Saliva, urine and serum were concomitantly collected from 4 healthy donors, and sEV were isolated from each respective biofluid, along with cfRNA from serum. sEVs were isolated from the respective biofluids via differential ultracentrifugation. Small RNA-sequencing was performed on each sample, and cluster analysis was performed based on ncRNA profiles. While some similarities existed in terms of sEV ncRNA cargo across biofluids, there are also notable differences in ncRNA class and ncRNA secretion, with each sEVs in each biofluid bearing a unique ncRNA profile. We conclude that sEV ncRNA cargo varies according to biofluid, so thus should be carefully selected and interpreted when designing translational or epidemiological studies.
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