Dataset Information

Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers worldwide. Therefore, current global research focuses on molecular tools for early diagnosis of HCC, which can lead to effective treatment at an early stage. Perilipin 5 (PLIN5) has been studied as one of the main proteins of the perilipin family, whose role is to maintain lipid homeostasis by inhibiting lipolysis. In this study, we show for the first time that PLIN5 is strongly expressed in tumors of human patients with HCC as well as in mouse livers, in which HCC was genetically or experimentally induced by treatment with the genotoxic agent diethylnitrosamine. Moreover, the secreted acute phase glycoprotein Lipocalin 2 (LCN2) established as a biomarker of acute kidney injury, is also proven to indicate liver injury with upregulated expression in numerous cases of hepatic damage, including steatohepatitis. LCN2 has been studied in various cancers, and it has been assigned roles in multiple cellular processes such as the suppression of the invasion of HCC cells and their metastatic abilities. The presence of this protein in blood and urine, in combination with the presence of ? -Fetoprotein (AFP), is hypothesized to serve as a biomarker of early stages of HCC. In the current study, we show in humans and mice that LCN2 is secreted into the serum from liver cancer tissue. We also show that AFP-positive hepatocytes represent the main source for the massive expression of LCN2 in tumoral tissue. Thus, the strong presence of PLIN5 and LCN2 in HCC and understanding their roles could establish them as markers for diagnosis or as treatment targets against HCC.

SUBMITTER: Asimakopoulou A

PROVIDER: S-EPMC6468921 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma.

Asimakopoulou Anastasia A Vucur Mihael M Luedde Tom T Schneiders Silvia S Kalampoka Stavroula S Weiss Thomas S TS Weiskirchen Ralf R

Cancers 20190319 3

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers worldwide. Therefore, current global research focuses on molecular tools for early diagnosis of HCC, which can lead to effective treatment at an early stage. Perilipin 5 (PLIN5) has been studied as one of the main proteins of the perilipin family, whose role is to maintain lipid homeostasis by inhibiting lipolysis. In this study, we show for the first time that PLIN5 is strongly expressed in tumors of human patients w ...[more]

PMID: 30893876

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Project description:Elevated lipocalin-2 (Lcn2) has been observed in multiple human cancers, but its biological roles remain unclear. Our purpose in this study was to investigate whether Lcn2 is involved in hepatocellular carcinoma (HCC) development via its involvement in invasion and metastasis. Using unsupervised hierarchical clustering analysis of tissue samples, we identified preferential expression of Lcn2 (>2-fold change) in the tumor group (differentiated group) versus the non-tumor group (liver cirrhosis group). LCN2 immunoreactivity was positively correlated with TNM stage (r = 0.194, P = 0.020), but not with differentiation or recurrence of HCC. Over-expression of Lcn2 was observed in HLK-2, HKK-2, and HLK-5 HCC cells. Knock-down of Lcn2 by shRNA in HKK-2 cells was correlated with the down-regulation of E-cadherin, CK-8, CK-18, and desmoplakin I/II (DesI/II) and the up-regulation of N-cadherin, vimentin (VIM), and fibronectin (FN), which are markers of the epithelial-mesenchymal transition (EMT) associated with tumor progression. The characteristics of EMT were reversed by adenoviral transduction of Lcn2 into SH-J1 cells. EGF or TGF-β treatment resulted in downregulation of Lcn2 with a concomitant change in EMT. Stable Lcn2 expression in HCC cells reduced the expression of the transcription factor Twist1, resulting in the inhibition of cell proliferation, migration, and invasion in vitro, and suppressed tumor growth and metastatic ability in a mouse model. These findings suggest that Lcn2 can reverse the EMT in HCC through transcriptional suppression of Twist 1. Thus, Lcn2 is a candidate metastasis suppressor and a potential therapeutic target for HCC. Unsupervised hierarchical clustering separated the samples into two main groups: a non-tumor group (NT, n = 40) and a HCC group (HCC, n = 40), and into two subgroups: a liver cirrhosis group (LC, n = 20) and a differentiated HCC group (difHCC, n = 20). Lcn2 was one of the unique genes with a two-fold or greater difference in expression from the mean with P < 0.01 based on the t-test for hierarchical clustering analysis.

Dataset Information

Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma.

Publications

Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma.

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