Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22635 | GEO | 2010/09/09
SECONDARY ACCESSION(S): PRJNA128193
REPOSITORIES: GEO
Similar Datasets
Project description:Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, i.e., whether they are derived from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major issue. Multiple HCC is clinically classified into intratumor metastasis (IM) and multicentric carcinogenesis (MC). Molecular markers differentiating IM and MC are of interest to clinical practitioners because clinical diagnosis of IM and MC often leads to different therapies. We analyzed multiple HCCs for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes, using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR. Comparative genomic hybridizaion experiments. A total of 20 tumor samples: ten pairs of HCC (from ten patients).
2010-09-08 | E-GEOD-22635 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
2019-01-03 | GSE112788 | GEO
Project description:Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
2019-01-03 | GSE113019 | GEO
Project description:Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
2019-01-03 | GSE113017 | GEO
Project description:Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
2019-01-03 | GSE112790 | GEO
Project description:Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC.
2016-04-30 | GSE79170 | GEO
Project description:Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC.
2016-04-30 | GSE79058 | GEO
Project description:Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis.
2020-12-22 | GSE153580 | GEO
Project description:Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis. Patients with diabetes mellitus (DM) have an epidemiologically higher risk for hepatocellular carcinoma (HCC). In mouse models, administration of streptozotocin (STZ) induces insulin-dependent DM by causing islet beta-cell dysfunction and also induced hepatocellular carcinoma (HCC) after 12 weeks. We attempted to elucidate the carcinogenic mechanism in the precancerous state by using hepatic miRNAs and create precancerous marker using exosomal miRNA. Serum and liver tissues were collected from STZ mice and non-treated mice (CTL mice) at 6, 10 and 12W. Total RNA in liver and exosome were extracted. Histological examination in liver in HE stain and hepatic and exosomal miRNA analysis were serially performed. miRNA and mRNA was analyzed by next-generation sequencing (NGS). The raw data of NGS was analyzed by Principal Component analysis. No inflammation or fibrosis was found in the liver in CTL mice during the observation period. In STZ-treated mice, regeneration and inflammation of hepatocytes was found at 6W and then nodules of atypical hepatocytes were found at 10 and 12 W. Expression of let-7f-5p, miR-21a-5p, 22-3p, and 26a-5p in liver of STZ mice was significantly increased during 6-10W, and these miRNAs controlled several tumor suppressor genes as target genes. We also identified six novel miRNAs associated with precancerous status. Furthermore, miR-122-5p and miR-192-5p in exosome were significantly upregulated in STZ mice in precancerous state. The expression of miRNAs that regulate tumor suppressor genes was enhanced even before carcinogenesis, and the expression of these miRNAs was not affected by liver fibrosis. In addition, the expression pattern of miRNAs in exosome is expected to be a marker for predicting carcinogenesis.
2020-12-22 | GSE153581 | GEO
Project description:Prevention and treatment options for hepatocellular carcinoma (HCC) are presently limited, underscoring the necessity for elucidating molecular mechanisms underlying HCC development and identifying new prevention and therapeutic targets. We demonstrate a unique precancerous niche that features enhanced p53 pathway, aberrant cytoplasmic p21WAF1/CIP1-expressing hepatocytes, and increased CD8+ T lymphocyte and macrophage infiltration in the livers of Ncoa5+/- mouse model of HCC. Metformin treatment reverses these precancerous features and profoundly reduces tumor incidence. Our data also reveal that a subset of HCC patients with a similar precancerous niche in the adjacent noncancerous livers had a relatively poor prognosis. Our study suggests a perceptible hepatic niche predisposing to HCC development and uncovers new actions of metformin in the prevention and treatment of HCC.
2020-03-28 | GSE110524 | GEO