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A common genetic trait through multistep hepatocarcinogenesis in a case with chronic hepatitis C

ABSTRACT: Common genetic traits are not well defined in hepatocellular carcinoma (HCC), because necroinflammation lasting long in prior to hepatocarcinogenesis embeds highly heterogenous genetic background in hepatocytes over the liver. We experienced a rare case with chronic hepatitis C, in which multiple liver tumors at different stages in multistep hepatocarcinogenesis were observed at the same time. Under the same genetic and etiological backgrounds, comparisons of expression profiles among dysplastic nodules (DN), well differentiated HCC (WEL), and moderately differentiated HCC (MOD) would provide critical genetic information for the initiation and progression of HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153565 | GEO | 2020/07/24

REPOSITORIES: GEO

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Project description:Surgical resection is the preferred treatment for Hepatocellular carcinoma; however, it induces tumor recurrence. Our objective was to understand the molecular mechanisms linking liver regeneration under chronic-inflammation to tumorigenesis. Mdr2-knockout mice, a model of inflammation-associated cancer, underwent partial-hepatectomy which led to enhanced hepatocarcinogenesis. Yet, liver regeneration in these mice was severely attenuated. We demonstrate the activation of the DNA damage response machinery and altered genomic instability during early liver inflammatory stages resulting in hepatocyte apoptosis and cell-cycle arrest, and suggest their involvement in tumor recurrence subsequent to partial hepatectomy. We propose that under the regenerative proliferative stress induced by liver resection, the genomic unstable hepatocytes generated during chronic-inflammation, escape apoptosis and reenter the cell-cycle, triggering the enhanced tumorigenesis At present, there is a great organ shortage worldwide, thus the main treatment for Hepatocellular carcinoma (HCC) is liver resection. However, liver resection induces recurrence and mortality. In our study, we decipher, for the first time, the contribution of the DNA damage response in HCC development and recurrence, the immediate and long term effect. This is an important finding regarding the association between carcinogenesis and DNA damage response. Additionally, we demonstrate yet another link between inflammation, inducing DNA damage and genome instability, and carcinogenesis that has not been explored in the past. These results may assist in developing treatments that will reduce tumor recurrence and additionally, new prophylactic therapies during early inflammatory stages. Keywords: time course, regeneration RNA was isolated from liver samples of 9-month-old Mdr2-/- and control mice obtained on days 0 (the removed lobe), 2 and 6 following PHx. Samples of d0 were obtained from the same mice that were sacrificed on later days. As we were concerned by the variability in the KO group 6 samples were obtained for d0. All other time points and groups contained 3 samples each.

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A common genetic trait through multistep hepatocarcinogenesis in a case with chronic hepatitis C

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