Dataset Information

MiRNA sequencing of serum exosomes from hepatocellular carcinoma and liver cirrhosis patients

ABSTRACT: miRNA sequencing of serum exosomes from hepatocellular carcinoma and liver cirrhosis patients

PROVIDER: PRJNA412166 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6076860.fastq.gz	Fastqsanger.gz
	SRR6076861.fastq.gz	Fastqsanger.gz
	SRR6076852.fastq.gz	Fastqsanger.gz
	SRR6076853.fastq.gz	Fastqsanger.gz
	SRR6076854.fastq.gz	Fastqsanger.gz

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Project description:Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in high risk population of cirrhotic patients.

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. *****************************************************************

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MiRNA sequencing of serum exosomes from hepatocellular carcinoma and liver cirrhosis patients

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