The long noncoding RNAs and mRNAs in the hepatocellular carcinoma at early and intermediate stage
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93789 | GEO | 2020/01/18
REPOSITORIES: GEO
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Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-05-29 | PXD006512 | Pride
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-03-01 | PXD008373 | Pride
Project description:Detection of HCC can improve the survival rate for patients with HCC. Thus, effective methods and biomarkers are required to improve the rate of early-HCC detection. We analyzed glycopeptides from AFP in the sera of patients with HCC and liver cirrhosis for the detection of HCC using LC-PRM with immunoprecipitation. Our results suggest that glycopeptide-based LC-PRM is a promising detection tool and that the relative percentage of fucosylated AFP is a clinically useful parameter for the detection of HCC.
2021-02-15 | MSV000086881 | MassIVE
Project description:Dysregulation of genes and associated mRNAs plays critical roles in the etiology and progression of hepatocellular carcinoma (HCC). Previous transcriptomic studies of HCC have been largely focused on Asian populations based on microarray platforms. Next generation-based RNA sequencing has provided an unparalleled power and opportunities to comprehensively characterize HCC at the whole transcriptome level.
2022-07-11 | GSE184733 | GEO
Project description:Ηepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early de-tection/diagnosis is vital for the prognosis of HCC whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on patient’s 6 month surveillance and use of at least two imaging modalities. The aim of this study was to investigate diagnostic markers for the detection of early HCC based on proteome analysis, microRNAs (miRNAs) and circulat-ing tumor cells (CTCs) in the blood of patients with cirrhosis, early and advanced HCC. We studied 89 patients with HCC of whom 33 had early HCC and 28 cirrhotic patients. CTCs were detected by Real-Time Quantitative Reverse Transcription PCR and immunofluorescence using the markers Epithelial cell adhesion molecule (EPCAM), Vimentin, A Fetoprotein (AFP) and surface major Vault protein (sMVP). Expression of the five most commonly HCC-involved miRNAs (miR-122, miR-200a, miR-200b, miR-221, miR-222) was examined in the serum by qRT-PCR. Finally patient serum was analyzed by whole proteome analysis (LC/MS). Twenty seven out of 53 (51%) patients with advanced HCC had detectable CTCs. Among them, 10/27 (37%) presented evidence of mesenchymal or intermediate stage cells (vimentin and/or sMVP positive). Moreover, 5/17 (29%) patients with early HCC and 6/28 (21%) cirrhotic patients had detectable CTCs. Patients with early and advanced HCC exhibited a significant increase of miR-200b when compared to cirrhotic patients. Our proteome analysis indicated that early HCC patients present a significant upregulation of APOA2, APOC3 proteins when compared to cir-rhotic patients, that when used in combination, cover the 100% of the patients with early HCC. In conclusion, miR-200b, APOA2 and APOC3 proteins are sensitive markers and can be poten-tially useful in combination for the early diagnosis of HCC.
2023-03-11 | PXD033306 | Pride
Project description:An increasing number of non-coding RNAs (ncRNAs) are implicated in various human diseases including cancer; however ncRNA transcriptome of hepatocellular carcinoma (HCC) remains largely unexplored. We use CAGE (Cap Analysis of Gene Expression) to comprehensively map transcription start sites (TSSs) across different etiologies of human HCC as well as mouse HCC, with particular emphasis on ncRNAs distant from protein-coding genes. We find thousands of significantly up-regulated distal ncRNAs in HCC tumors compared to their matched non-tumors, which are as many as protein-coding genes. Moreover, we identify many LTR retroviral promoters activated in HCC tissues and expressed in a subfamily-specific manner, which account for approximately 20% of the up-regulated distal ncRNAs. The transcripts derived from LTRs, determined by 3' RACE, are multi-exon nuclear ncRNAs typically 0.5-2kb in length. This study sheds light on ncRNA transcriptome of human and mouse HCC. Expression profiles using CAGE for 37 mouse HCC. The human data are archived at dbGaP (phs000885.v1.p1). An umbrella BioProject has been created to associate the GEO and dbGaP BioProjects: PRJNA278792
2015-09-10 | E-GEOD-60982 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is considered the result of a stepwise carcinogenic process, more often beginning with development of premalignant lesions within a cirrhotic liver, morphologically characterized by low- (LGDN) and high-grade (HGDN) dysplastic nodules. Piwi-interacting RNAs (piRNAs) represent a large family of small noncoding (snc) RNAs, 23-35 nucleotide-long, first identified in fruitfly germline cells by their ability to interact with PIWI proteins and thereby exert epigenetic and post-transcriptional regulation of gene expression. The PIWI-piRNAs pathway is active also in human somatic tissues, including stem and cancer cells, where piRNAs and piRNA-like molecules have been shown to influence key cellular processes. We applied small RNA sequencing to search for human liver piRNAs and to profile their expression patterns in cirrhotic nodules (CNs), LGDN, HGDN, early HCC (eHCC) and progressed HCC (pHCC), aiming at identifying possible relationships between these sncRNAs and liver carcinogenesis. Analyzing 54 nodules (14 CN, 8 LGDN, 6 HGDN, 6 eHCC and 20 pHCC) from 17 patients, we identified a 125 piRNA expression signature that clearly discriminates HCC from matched CNs, correlating also to clinicopathological characteristics of HCC. This result was confirmed by functional analysis of predicted piRNA target mRNAs. Interestingly, 24 piRNAs showed specific expression patterns in dysplastic nodules, respect to cirrhotic liver and/or pHCC. These results demonstrate that the piRNA pathway is active in human liver, where it is likely to represent a new player in the molecular events that characterize hepatocellular carcinogenesis, from early stages to pHCC. Furthermore, they suggest that piRNAs might represent new disease biomarkers, potentially useful for differential diagnosis of dysplastic and neoplastic liver lesions.
2016-07-15 | E-MTAB-3973 | biostudies-arrayexpress
Project description:Multi-omics approaches were utilized to comprehensively analyze the molecular characteristics of hepatocellular carcinoma (HCC) in South Texas (STX) Hispanics. Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1, suggesting a predominant activation of the Wnt/beta-catenin pathway. Cell cycles were positively-, and liver functions were negatively-enriched on gene set enrichment analysis of our transcriptomic and proteomic datasets. Enrichments of gene sets representing specific liver metabolic pathways were found to be associated with the dysregulation of corresponding metabolites. Significant reduction of the majority of lipids seen in serum samples of HCC patients and many fatty acids in HCC tumors corroborate negative adipogenesis and lipid metabolism enrichments. We identified two subtypes of HCC using enrichment scores from paired tumor-nontumor samples of STX-Hispanics or TCGA-LIHC. The subtype with better overall survival revealed pronounced positive enrichments of immune-, angiogenesis-, and negative enrichments of liver function-related hallmark gene sets than the other. The former had higher levels of immune checkpoint and immune exhaustion markers. Together, we report molecular features of HCC, specific and non-specific to Hispanics.
2023-07-11 | MSV000092403 | MassIVE
Project description:To explore the potential involvement of lncRNAs in hepatocellular carcinoma (HCC) oncogenesis, we conducted lncRNA and mRNA profiling in 3 pairs of human HCC and adjacent normal tissue (NT) by microarray. With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, the number of lncRNAs and coding transcripts that could be detected here is 10,149 and 14,944, respectively. From the data, thousands of lncRNAs and mRNAs were found to bedifferentially expressed (Fold Change≥2.0) in HCC tissues compared with NT and identified 624 lncRNAs and 1050 mRNAs were differentially expressed in all three HCC tissues.Bioinformatic analysis (gene ontology, pathway and network analysis) was performed for further study of these differentially expressed mRNAs.By qRT-PCR analysis in nineteen pairs HCC and adjacent normal tissues, we found that eightl ncRNAs were aberrantly expressed in HCC compared with corresponding NT, which is consistent with microarray data. Additionally, change trends of seven lncRNAs were basically identical to their nearby coding genes. In this study, to explore the potential involvement of lncRNAs in hepatocellular carcinoma (HCC) oncogenesis, we conducted lncRNA and mRNA profiling in 3 pairs of human HCC and adjacent normal tissue (NT) by microarray.
2014-02-21 | E-GEOD-55191 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.
| S-EPMC7649909 | biostudies-literature