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Plasma-derived extracellular vesicles from patients with liver cirrhosis and hepatocellular carcinoma

ABSTRACT: Quantitative label-free proteomic analysis of extracellular vesicles. A pool of isolated proteins from extracellular vesicles (EVs) was performed for each sample group, namely healthy participants (HP), liver cirrhosis (LC), and hepatocellular carcinoma (HCC), split into three biological replicates. Then, samples were digested with trypsin, and the peptides were subjected to Nano LC-MS/MS Analysis and Mass Spectrometry. Nine raw MS files were analyzed and searched against the human protein database based on the species of the samples using Maxquant. The parameters were set as follows: the protein modifications were carbamidomethylation (C) (fixed), oxidation (M) (variable); the enzyme specificity was set to trypsin; the maximum missed cleavage was set to 2; the precursor ion mass tolerance was set to 10 ppm, and MS/MS tolerance was 0.5 Da.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: PhD. Verónica Rocío Vásquez-Garzón

PROVIDER: PXD047723 | JPOST Repository | Tue Jul 09 00:00:00 BST 2024

REPOSITORIES: jPOST

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Project description:In cancer management, early and accurate diagnosis of hepatocellular carcinoma (HCC) is important for enhancing survival rate of patients. Currently, serum alpha-fetoprotein (AFP) is the only one biomarker for detection of HCC. However, serum AFP is not satisfactory for diagnosis of HCC due to its low accuracy (about 60-70%). In this study, we collected 109 serum samples (discovery set) from healthy control (HC) and patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC, and analyzed them with custom lncRNA microarray. Profiling analysis shows 181 differentially expressed lncRNAs between HCs and patients with CHB, LC and HCC. Then a 48-lncRNA diagnostic signature was identified with 100% predictive accuracy for all subjects in the discovery set. This diagnostic signature was verified with a cross-validation analysis in the discovery set. To further corroborate the signature, we gathered another 66 serum samples (validation set) and also analyzed them with microarray. The result indicates that the same signature has similar diagnostic accuracy for HC (100%), CHB (73%), LC (88%) and HCC (95%), implying a reproducible diagnostic biomarker for HCC. Receiver operating characteristic (ROC) analysis exhibits that this signature has significantly higher diagnostic accuracy for HCC and non-cancerous subjects (area under curve [AUC]: 0.994) than AFP (AUC: 0.773) in the discovery set and this was also verified in the validation set (0.964 vs 0.792). More importantly, the signature detected small HCC (<3cm) with 100% (13/13) accuracy while AFP with only 61.5% (8/13). Altogether, this study demonstrates that the serum 48-lncRNA signature is not only a powerful and sensitive biomarker for diagnosis of HCC but also a potential biomarker for LC. ***************************************************************** Submitter declares these data are subject to patent number ZL 2016 1 0397094. *****************************************************************

			Action	DRS
	EVs_HCC01.raw	Raw
	EVs_HCC02.raw	Raw
	EVs_HCC03.raw	Raw
	EVs_HP01.raw	Raw
	EVs_HP02.raw	Raw

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Plasma-derived extracellular vesicles from patients with liver cirrhosis and hepatocellular carcinoma

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