Unique MicroRNA Expression Signature Predicts Survival, Metastases and Recurrence of HCC
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE6857 | GEO | 2008/01/14
SECONDARY ACCESSION(S): PRJNA99101
REPOSITORIES: GEO
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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: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.
2012-03-20 | GSE36376 | GEO
Project description:Genetic variations play an important role in tumor development and metastasis. Hepatocellular carcinoma (HCC) is one of leading cause of cancer-related death. Despite improvements in surveillance and clinical treatment strategies, the prognosis of HCC remains dismal. Affymetrix SNP 6.0 array were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent liver transplantation. Recurrence related SNPs were selected and validated. Affymetrix SNP 6.0 arrays were performed according to the manufacturer's directions on DNA extracted from formalin-fixed paraffin-embedded HCC tissues
2012-10-26 | E-GEOD-29667 | 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: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) can be offered to patients beyond Milan criteria. However, there are currently no molecular markers that can be used on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to identify proteins on HCC explant predictive of recurrence post-transplant, thereby guiding surveillance strategies and identifying patients beyond Milan criteria who would fare well following LT. Methods: LT recipients who had been transplanted at the University Health Network for HCC beyond Milan criteria in the context of Hepatitis B cirrhosis were identified. Snap-frozen samples from the dominant tumors of recurrent (N=7) and non-recurrent (N=4) patients were analyzed using LC-MS/MS on a Q-Exactive Plus mass spectrometer to delineate a distinctive proteomic signature. These tumors were also profiled by a Human Gene 2.0 ST microarray platform to identify a transcriptomic signature predictive of recurrence and analyzed with R packages. STRING database was used to characterize the implicated pathways. Kaplan-Meier estimator was used to generate a combined proteomic/transcriptomic signature predictive of HCC recurrence in patients with HCC beyond Milan criteria at time of LT. Significantly predictive proteins were verified and internally validated by immunoblotting or immunohistochemistry. Results: A total of 79 proteins and 636 genes were significantly differentially expressed in recurrent HCC, compared to non-recurrent (p<0.05). Among these, LGALS3, LGALS3BP, HAL, THBS1, and BLMH, were significantly increased in recurrent HCC at the protein and gene expression level. In turn, ALDH1A1 protein and gene expression were significantly decreased in recurrent HCC. Univariate survival analysis depicted ALDH1A1 (HR=0.084, 95%CI 0.01-0.68, p=0.02), LGALS3BP (HR=7.14, 95%CI 1.20-42.96, p=0.03), and LGALS3 (HR=2.89, 95%CI 1.01-8.3, p=0.049) as the key dysregulated proteins and genes in the patients with HCC recurrence versus those with non-recurrence by both proteomic and transcriptomic analysis. Decreased ALDH1A1 and significantly increased LGALS3 protein expression in recurrent HCC was verified by immunoblotting. Increased LGALS3BP protein expression in recurrent HCC was orthogonally verified and validated by immunohistochemistry in 30 independent HCC samples. Conclusion: Protein and gene expression of the cancer stem cell marker ALDH1A1 was protective against cancer recurrence in patients transplanted for HCC beyond Milan criteria. Conversely, increased expression of LGALS3 and LGALS3BP on explant was significantly predictive of post-transplant recurrence. These findings were internally validated, suggesting potential utility in identifying patients with HCC beyond Milan who would clearly benefit from transplant with limited recurrence risk and guiding post-transplant surveillance.
2022-02-22 | PXD022881 | Pride
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: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 & AIMS: Despite the increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the balance of the tumor-associated myeloid response and its translational value. We aimed to construct a simple and reliable signature of local myeloid responses in hepatocellular carcinoma (HCC). METHODS: Using in situ immunohistochemistry (IHC), we assessed myeloid features that revealed the distribution of major myeloid subtypes in both the peri- and intratumoral regions of HCC. A signature was constructed using an L1-penalized Cox regression model based on the postsurgery recurrence data from a training subset (n = 244) that was validated in the testing subset (n = 244) and independent internal (n = 341) and external (n = 348) cohorts. Multiplexed immunofluorescence staining, flow cytometry and transcriptomic analyses were performed to examine the immunological deviations associated with the myeloid signature. Further, we built nomograms to provide a more robust and personalized prognosis for HCC patients. RESULTS: A 2-feature-based, myeloid-specific prognostic signature, namely the myeloid response score (MRS), was constructed. The increase in the MRS was associated with a change in the predominant myeloid populations from CD169+ macrophages (Mφs) in MRSlow HCCs to CD15+CD11b+ neutrophils and CD11b+CD169- Mφs in MRShigh tumors, suggesting a shift in the balance of the myeloid response from antitumor to protumor activities. This alteration was also accompanied by the enhancement of CD8+ T cell exhaustion patterns, including impaired cytotoxic potential and elevated programmed cell death protein 1 (PD-1) expression. The MRS and the MRS-based nomograms had higher accuracy for predicting recurrence and patient survival than the Barcelona Clinic Liver Cancer (BCLC) and tumor-node-metastasis (TNM) staging systems and were validated in a multicenter cohort of HCC patients. Moreover, in a separate cohort of 51 patients, we provided evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC. CONCLUSIONS: We identified and validated a descriptive and prognostic myeloid signature for HCC. HCC tissues with low, intermediate, and high MRS estimates represent tumors with immunocompetent, immunodeficient, and immunosuppressive subtypes, respectively. This technically simple and reliable myeloid signature shows remarkable prognostic potential for HCC after resection and could serve as the basis for the stratification of HCC immune subtypes to aid in a wide range of clinical decisions.
2019-07-27 | GSE134921 | GEO
Project description:The variability in the prognosis of hepatocellular carcinoma (HCC) patients suggests that HCC may comprise several distinctive biological phenotypes. These phenotypes may result from different neoplastic pathways during the tumorigenesis and/or from a different cell of origin. Here we address if the transcriptional characteristics of the HCC would provide insight into the cellular origin of the tumors. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes, HCC from mouse models, and human HCC. The HCC patients who shared gene expression patterns with fetal hepatoblasts showed extremely poor prognosis when compared with those lacking the hepatoblast signature. The gene expression program that distinguishes this novel subtype from the rest of HCC includes well known markers of hepatic oval cells, suggesting that HCC in this subtype may arise from hepatic progenitor cells. Two independent gene network analyses of the gene expression signature characteristic for the tumors sharing the hepatoblast expression patterns revealed that activation of AP-1 transcription factors might play key roles in tumor development in the newly identified HCC subtype. In addition, by applying hepatoblast-specific and genome-wide global signatures, HCC patients were further stratified into three distinct subgroups with a significant association with overall survival and recurrence. Total RNAs from 19 normal livers were pooled and used as the reference for all microarray experiments. To obtain gene expression profile data from 49 human HCC, 20 µg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using a dye-swap strategy to eliminate dye labeling bias.
2010-07-01 | E-GEOD-4024 | biostudies-arrayexpress