ABSTRACT: Copy Number Variation of human hepatocellular carcinoma (HCC) and Cholangiocarcinoma (CCA) from the Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)
Project description:<p>Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We performed targeted sequencing of Thai ICC and HCC among the Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC) cohort using the OncoVar platform.</p>
Project description:We used Affymetrix SNP6.0 microarray profiling to analyze Copy Number Variation in tumor and paired non-tumor tissue of HCC and CCA patients. We used copy number data to confirm molecular subgroups of HCC and CCA patients from Thailand
Project description:Human hepatocellular carcinoma (HCC) and Cholangiocarcinoma (CCA) from Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)
Project description:Gene expression data of human hepatocellular carcinoma (HCC) and Cholangiocarcinoma (CCA) from Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)
Project description:We compared transcriptomic profiles of ICC tumor specimens to hepatocellular carcinoma (HCC) specimens using Affymetrix mRNA array and the miRNA array platforms to search for unique gene signatures linked to patient prognosis. ICC and HCC share common stem-like molecular characteristics and stem-like tumor features associated with poor prognosis. Gene expression profiling of 16 intrahepatic cholangiocarcinoma (ICC), 7 mixed type of combined hepatocellular cholangiocarcinoma (CHC), 2 Hepatic adenoma, 3 focal nodular hyperplasia (FNH), 5 non-tumor liver tissues, and 2 CCA cell lines were performed.
Project description:Introduction: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a mixed-type tumor of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which is classified into classical type (i.e., c-CHC) and intermediate cell type (i.e., i-CHC). c-CHC harbors both HCC and iCCA cells, whereas i-CHC is comprised of intermediate cell types lacking classical regions of HCC or iCCA cells. Notwithstanding the unique pathological feature of i-CHC, its molecular characteristics is not fully elucidated yet. Methods: To obtain molecular insights on the i-CHC, RNA-sequencing (RNA-Seq) and whole genome sequencing (WGS) profiling were performed on the tissues of i-CHC, HCC, and iCCA, respectively. Results: i-CHC showed unique transcriptomic features differing from HCC and iCCA, showing higher expression of Notch signaling and frequent splicing events of intron-retention (IR). Noticeably, we found that i-CHC had DNA-copy number loss and concomitant transcriptional suppression of METTL16, which may contribute to the aggressive progression of i-CHC via Notch activation. Conclusions: We suggest that i-CHC had unique transcriptomic features, providing new insights into the pathobiology of i-CHC.
Project description:Mixed hepatocellular – cholangiocarcinoma (HCC-CCA) is a highly malignant primary liver cancer of increasing incidence for which the cell of origin and molecular pathogenesis have not yet been fully elucidated. Here, by linking YFP to the progenitor cell specific promoter of Foxl1 in Mdr2-KO mice, we generated a lineage tracing mouse model for liver cancer to monitor the development of mixed HCC-CCA tumors following a prolonged period of liver inflammation. In this model of chronic hepatitis, we demonstrate that liver progenitor cells are the source of mixed HCC-CCA tumors but not of hepatocellular carcinoma (HCC). Moreover, we show that IL6, originating from senescent hepatic cells, is involved in progenitor cell proliferation and development of mixed HCC-CCA tumors via IL6 trans-signaling. These findings could form the basis for the development of novel therapeutic approaches for treatment of mixed HCC-CCA liver cancer.
Project description:Mixed hepatocellular – cholangiocarcinoma (HCC-CCA) is a highly malignant primary liver cancer of increasing incidence for which the cell of origin and molecular pathogenesis have not yet been fully elucidated. Here, by linking YFP to the progenitor cell specific promoter of Foxl1 in Mdr2-KO mice, we generated a lineage tracing mouse model for liver cancer to monitor the development of mixed HCC-CCA tumors following a prolonged period of liver inflammation. In this model of chronic hepatitis, we demonstrate that liver progenitor cells are the source of mixed HCC-CCA tumors but not of hepatocellular carcinoma (HCC). Moreover, we show that IL6, originating from senescent hepatic cells, is involved in progenitor cell proliferation and development of mixed HCC-CCA tumors via IL6 trans-signaling. These findings could form the basis for the development of novel therapeutic approaches for treatment of mixed HCC-CCA liver cancer.
Project description:We used Affymetrix HTA2.0 microarray profiling to analyze gene expression patterns in tumor and paired non-tumor tissue of HCC and CCA patients. We used microarrays data to identified molecular subgroup of HCC and CCA patients from Thailand
Project description:FBXO32 is upregulated in multiple human cancers, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), and correlated to poor prognosis. Moreover, we demonstrated the tumor-promoting function in these cancers. Here, to explore the associated molecular mechanism of FBXO32 in tumor development, the RNA-seq of FBXO32-knockout Huh7 cells was investigated and analyzed
