Invasion and metastasis related long non-coding RNA expression profiles in hepatocellular carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67260 | GEO | 2015/03/26
SECONDARY ACCESSION(S): PRJNA279381
REPOSITORIES: GEO
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Project description:Vascular invasion is considered as the critical risk factors for tumor recurrence of hepatocellular carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular invasion (MaVI) and metastasis in HCC, we performed an iTRAQ based proteomic study to identify notably dysregulated proteins in 53 HCC patients with differential vascular invasion. In patients with MaVI, 47 proteins were significantly down-regulated in HCC tumor tissue. More importantly, 30 of them were not changed in HCC without MaVI. Gene ontology analysis of these 47 proteins shows the top 3 enriched pathways are urea cycle, gluconeogenesis and arginine biosynthetic process. We validated 9 remarkably dysregulated candidates in HCC patients with MaVI by Western blot, including 8 down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, Annexin A6 and CES1) and 1 up-regulated protein (CKAP4). Furthermore, dysregulation of CPS1, ASL and ARG1, key enzymes involved in urea cycle, together with Annexin A6 and CES1, major proteins in regulating cholesterol homeostasis and fatty acid ester metabolism were verified using immunohistochemical staining. The significant down-regulation of urea cycle generates clinically relevant proteomic signature in HCC patients with macrovascular invasion, which may provide possible insights into the molecular mechanisms of metastasis and new therapeutic targets of HCC.
2022-03-02 | PXD011846 | Pride
Project description:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. It is crucial to identify patients with a high risk of recurrence and develop more intensified or targeted treatment strategy to improve disease outcome. In the training set, tumor and non-tumor liver were profiled separately, and each was used to generate a prediction model which was validated with the use of independent validation set.
2012-03-20 | E-GEOD-36376 | biostudies-arrayexpress
Project description:Background: The presence of vascular invasion (VI) in pathology specimens has been widely described as closely linked to poor outcome in hepatocellular carcinoma (HCC) patients after tumor resection. Previous attempts have been conducted to achieve molecular markers or signatures to predict HCC recurrence in HCC. Here, we aim to develop a diagnostic model combining clinical and genomic variables able to detect the presence of VI prior to surgery and link it to survival estimation. Methods: Seventy-nine HCV related HCC samples from patients that underwent surgical resection as a treatment for HCC were subjected to Genome-wide gene expression profiling and a predictive model of vascular invasion was constructed. The model was tested in an independent-validation set of 153 fixed tissue samples of resected HCC. Quantitative RTPCR and inmunohistochemistry were performed in HCC samples to test a potential biomarker. Results: A 39-gene signature was able to accurately (72%) identify vascular invasion in HCC patients treated with resection. A model including tumor size and the signature is able to predict presence of VI with 85% accuracy in HCV-related HCC patients, and is able to exclude VI in up to 87% cases in HCC from all etiologies. Conclusions: Using the VI gene signature together with tumor size, VI can be successfully detected in HCC patients. The diagnostic model, integrated in a previously reported survival chart is able to provide an estimated survival for selected cases. Clinical implications of this fact are relevant to provide objective data to further apply expanded indication of curative treatments in HCC. Gene-expression profiling was performed using formalin-fixed, paraffin-embedded hepatocellular carcinoma tissues obtained at the time of surgical resection.
2011-07-30 | E-GEOD-20017 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for approximately 90%, and it has a five-year survival rate around only 30–40%. Similar to other kinds of cancers, tumor metastasis remains the primary cause of mortality of HCC patients. It is well known that metastasis is a multistage process that requires cancer cell detachment from the primary tumor, survival in the circulation, settlement at distant sites and growth. During this process, metastatic cells go through detachment, migration, invasion and adhesion, and inhibition of any one of these steps has the potential to block the entire metastatic process. However, there is very little advancement in the area of blocking tumor metastasis, therefore, new effective agents possessing anti-metastasis activities are urgently needed for better prevention and treatment of HCC and other cancers. Our previous results suggested that EPS11, a novel marine bacterial polysaccharide, might be a potential drug candidate for human non-small cell lung carcinoma treatment. In this study, we further investigate the anticancer mechanisms against liver cancer and the anti-metastatic effects of EPS11.
2022-02-17 | PXD025155 | Pride
Project description:In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence. Keywords: disease state design Gene expression profiles were conducted in primary HCC and corresponding noncancerous hepatic tissues from 244 Chinese HCC patients. A total of 134 well-defined cases were used as a training group. Among them, 30 had primary HCC lesions accompanied by tumor emboli and 104 had solitary HCC with no metastasis/recurrence found at follow-up (3 yr). We used a testing group of 110 independent cases. The testing cases included 43 multinodular and 67 solitary HCC. In addition, eight normal liver tissues from disease-free patients were included as normal controls. In the analysis of the 244 HCC cases, RNA was isolated in a pairwise fashion from tumor or non-tumor tissue and samples were selected in random order for miRNA analysis to avoid grouping bias.
2008-01-14 | E-GEOD-6857 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is one of the leading causes of mortality related to cancer all over the world. The poor prognosis of HCC is mostly due to recurrence and tumor metastasis. In order to better understand the molecular mechanisms of HCC metastasis, we analyzed the proteome of three HCC cell lines with different metastasis potentials by using quantitative proteomics and bioinformatics analysis. As a result, we identified 331 cellular proteins potentially associated to HCC metastasis, and constructed a highly connected protein-protein interaction (PPI) network. Functional annotation of the network uncovered prominent pathways and key roles of these proteins, suggesting that metabolism and cytoskeleton biological progresses are greatly involved with HCC metastasis. Furthermore, integrative network analysis revealed a rich-club organization in the PPI network indicating a hub center of connections, including several well-known cancer related proteins, such as SRC proto-oncogene, non-receptor tyrosine kinase (SRC) and pyruvate kinase M2 (PKM2). Moreover, the differential expressions of two identified proteins, including PKM2 and actin-related protein 2/3 complex subunit 4 (ARPC4), were validated using Western blotting. These two proteins were identified as potential prognostic markers for HCC by using survival rate analysis.
2017-06-20 | PXD005647 | Pride
Project description:Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process. We sorted CD13+CD133+ and CD13-CD133- cells from Hep3B, Huh7, and PLC/PRF/5 HCC cell lines as liver CSCs and non-CSCs, then hybridized on Affymetrix microarrays. We sought to identify distinct lncRNAs in liver CSCs.
2015-03-05 | E-GEOD-66529 | biostudies-arrayexpress
Project description:Non-coding microRNAs (miRNAs) mainly regulate the expression of targeted genes by regulating mRNA degradation or repressing their protein translation. Recent research has shown miRNAs to have remarkable potential as biomarkers for the diagnosis and prognosis of disease. Since vascular invasion (VI) provides a direct path for solid tumor metastasis/recurrence, in this study we investigated if miRNAs can serve as a biomarker to differentiate between VI- and VI+ tumors. MiRNA microarray profiling was then performed on 172 human HCC tumors samples with or without VI from HCC patients.
2015-03-23 | GSE67139 | GEO
Project description:Non-coding microRNAs (miRNAs) mainly regulate the expression of targeted genes by regulating mRNA degradation or repressing their protein translation. Recent research has shown miRNAs to have remarkable potential as biomarkers for the diagnosis and prognosis of disease. Since vascular invasion (VI) provides a direct path for solid tumor metastasis/recurrence, in this study we investigated if miRNAs can serve as a biomarker to differentiate between VI- and VI+ tumors. MiRNA microarray profiling was then performed on 172 human HCC tumors samples with or without VI from HCC patients.
2015-03-23 | GSE67138 | GEO
Project description:Background: The presence of vascular invasion (VI) in pathology specimens has been widely described as closely linked to poor outcome in hepatocellular carcinoma (HCC) patients after tumor resection. Previous attempts have been conducted to achieve molecular markers or signatures to predict HCC recurrence in HCC. Here, we aim to develop a diagnostic model combining clinical and genomic variables able to detect the presence of VI prior to surgery and link it to survival estimation. Methods: Seventy-nine HCV related HCC samples from patients that underwent surgical resection as a treatment for HCC were subjected to Genome-wide gene expression profiling and a predictive model of vascular invasion was constructed. The model was tested in an independent-validation set of 153 fixed tissue samples of resected HCC. Quantitative RTPCR and inmunohistochemistry were performed in HCC samples to test a potential biomarker. Results: A 39-gene signature was able to accurately (72%) identify vascular invasion in HCC patients treated with resection. A model including tumor size and the signature is able to predict presence of VI with 85% accuracy in HCV-related HCC patients, and is able to exclude VI in up to 87% cases in HCC from all etiologies. Conclusions: Using the VI gene signature together with tumor size, VI can be successfully detected in HCC patients. The diagnostic model, integrated in a previously reported survival chart is able to provide an estimated survival for selected cases. Clinical implications of this fact are relevant to provide objective data to further apply expanded indication of curative treatments in HCC.
2011-07-31 | GSE20017 | GEO