Serum proteomics and metabolomics reveal novel noninvasive molecular signatures for hepatocellular carcinoma diagnosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Qishui Ou
PROVIDER: PXD076855 | iProX | Fri Apr 10 00:00:00 GMT+01:00 2026
REPOSITORIES: iProX
Similar Datasets
Project description:This study aimed to identify and validate noninvasive serum protein and metabolite biomarkers for the early detection and prognostic assessment of hepatocellular carcinoma (HCC).In this study, we systematically analyzed serum proteomics and metabolomics across four cohorts, including healthy controls (Health) and patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and HCC. Standardized sample handling protocols were applied, and high-resolution mass spectrometry combined with rigorous statistical analyses was used to identify differential proteins and metabolites.
2026-04-10 | MTBLS14248 | MetaboLights
Project description:BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.
2013-01-22 | GSE15654 | GEO
Project description:Background: Of Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), 85%-90% of cases develop from liver cirrhosis, and circular RNAs (circRNAs) have important roles in this process; however, differences in serum circRNA expression profiles between patients with HBV-related cirrhosis and those with HCC have not been studied. Methods: Serum RNA was extracted from patients with HCC and cirrhosis (n = 5 per group) and used for microarray analysis of circRNA expression profiles. Bioinformatics analyses, including clustering, differential expression, and construction of a ceRNA network, were performed. Quantitative real-time reverse transcription PCR validation analysis was conducted using samples from patients with HBV-related cirrhosis (n = 88) and HCC (n = 73). Further, statistical analyses were used to analyze the potential function and value of selected circRNAs with expression differing between the HBV-related cirrhosis and HCC groups. Results: Cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs. Further, qRT-PCR analysis showed that circRNA_0000367 expression was consistent with that detected by microarray experiments, with significantly lower levels in patients with HBV-related HCC than those with HBV-related cirrhosis. CircRNA_0000367 expression levels were also significantly lower in patients with drug-resistant HBV and those with HBV-related cirrhosis with Model for End-Stage Liver Disease score < 10. Further, circRNA_00000367 expression levels were lower in patients with HBV-related cirrhosis who progressed to HCC. Analysis of the lncRNA-miRNA-mRNA ceRNA network identified 39 miRNAs and 24 mRNAs involved in circRNA_00000367 networks; these target genes were involved in various biological processes and signaling pathways. Conclusion: Serum cicrRNA_0000367 is a potential HCC biomarker in patients with HBV-related cirrhosis, where down-regulation of cicrRNA_0000367 in HBV-related cirrhosis may be associated with progression to HCC.
2025-02-10 | E-MTAB-12717 | biostudies-arrayexpress
Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens
2013-01-22 | E-GEOD-15654 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC. 156 primary tissues and 25 cultured normal and HCC cell lines
2014-09-16 | E-GEOD-60753 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is ranked second in cancer-associated deaths worldwide. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). It is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations.
2014-12-31 | GSE62232 | GEO
Project description:We sought to identify sensitive and noninvasive biomarkers for development and progression of post HBV infection liver cirrhosis.
2019-12-01 | GSE123932 | GEO
Project description:Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (PSAP, MMRN2, CAPNS1, CDH1, TIPRL, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC.
2025-02-25 | PXD050099 | JPOST Repository
Project description:The aim of this study is to compare post-hepatitis C virus (HCV) and post-alcoholism cirrhosis gene expression profiling. By transcriptome analysis with a cDNA array virtually covering every transcript in liver, we compared transcript levels in alcoholic- , HCV-cirrhosis and control liver. A stringent selection identified a list of 70 transcripts which completely separated the 3 groups of patients (7 HCV-cirrhosis, 7 alcoholic cirrhosis and 8 control livers). In contrast, in an hepatocellular carcinoma (HCC) context, comparison of 10 HCV-cirrhosis, 10 alcoholic cirrhosis and the 8 control livers failed to identify such transcripts. We report that dysregulations at the transcriptional level do exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC. Keywords: etiology-dependent and HCC-dependent analysis
2008-02-01 | GSE10356 | GEO
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC.
2014-09-16 | GSE60753 | GEO