Dataset Information

Enhancing Concurrent Chemoradiation Outcome Prediction for Locally Advanced Cervical Cancer Patients Through Plasma Extracellular Vesicle Proteomics Analysis

ABSTRACT: Majority of the patients with cervical cancer present with locally advanced cervical cancer (LACC), which is primarily treated using concurrent chemoradiation (CCRT) and lacks reliable predictive biomarkers. Extracellular vesicles (EVs) could potentially define the dynamic biological response to CCRT. However, the relationship between EVs and the therapeutic response to LACC is unestablished. This study aimed to determine the relationship of plasma EVs pre- and post-CCRT in 62 patients with LACC. EVs were isolated using ultracentrifugation (UC) with size exclusion chromatography or UC alone for proteomic analyses. The plasma particle concentration significantly increased post-treatment in non-responders. The viral control process was enhanced at 1 month and adaptive immune response increased at 3 months, following the standard clinical cut-off. Sparse partial least squares-discriminant analysis revealed 8, 13, and 19 proteins at diagnosis, 1 month, and 3 months, respectively, influencing the CCRT response. Among these, FIBG, TFR1, HBA, and FINC, are poor prognostic markers in the cancer genome atlas tissue gene expression database. The discriminant model demonstrated excellent specificity and negative predictive value. In conclusion, the validation of our model underscores its reliability in determining the responsiveness to CCRT, highlighting the potential clinical applicability of EVs in improving outcomes in LACC.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: L Kittinun

PROVIDER: PXD050754 | JPOST Repository | Mon Sep 30 00:00:00 BST 2024

REPOSITORIES: jPOST

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Enhancing outcome prediction of concurrent chemoradiation treatment in patients with locally advanced cervical cancer through plasma extracellular vesicle proteomics.

Leetanaporn K K Chiangjong W W Roytrakul S S Molika P P Janmunee N N Atjimakul T T Hanprasertpong J J Navakanitworakul R R

Heliyon 20240822 16

Most patients with locally advanced cervical cancer (LACC) are primarily treated using concurrent chemoradiation (CCRT); however, LACC lacks reliable predictive biomarkers. Extracellular vesicles (EVs) could define the dynamic biological response to CCRT. However, the relationship between EVs and the therapeutic response to LACC is unestablished. Thus, we aimed to determine the relationship of plasma EVs pre- and post-CCRT in 62 patients with LACC. For proteomic analyses, EVs were isolated using ...[more]

PMID: 39262965

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.

			Action	DRS
	UC.7z	Other
	UC.csv	Csv
	USEC.csv	Csv
	USEC_raw.7z	Other