Malic enzyme 1 is a potential marker of combined hepatocellular cholangiocarcinoma, subtype with stem‐cell features, intermediate‐cell type

Abstract

Aim Combined hepatocellular cholangiocarcinoma, subtype with stem‐cell features, intermediate‐cell subtype (INT) shows various histological appearances and could be misdiagnosed as intrahepatic cholangiocarcinoma (iCCA). In the present study, we aimed to identify specific histological diagnostic markers of INT. Methods We extracted RNA from FFPE sections of six INT, five iCCA, and five hepatocellular carcinoma (HCC) cases and compared gene expression between INT, iCCA, and HCC by microarray analysis. We then undertook immunohistochemical (IHC) staining of potential key molecules identified by microarray analysis, the conventional hepatocytic marker, hepatocyte paraffin (HepPar)‐1, and the cholangiocytic markers, keratin (K) 7 and K19, on 35 INT, 25 iCCA, and 60 HCC cases. Results Microarray analysis suggested that malic enzyme 1 (ME1) was significantly upregulated in INT. Immunohistochemical analysis revealed that the positive rates of ME1 in INT, iCCA, and HCC were 77.1% (27/35), 28.0% (7/25), and 61.7% (37/60), respectively. Analysis of classification and regression trees based on IHC scores indicated that HepPar‐1 could be a good candidate for discriminating HCC from the others with high sensitivity (93.3%) and high specificity (96.7%). A multiple logistic regression model and receiver operating characteristic curve analysis based on the IHC scores of ME1, K7, and K19 generated a composite score that can discriminate between INT and iCCA. Using this composite score, INT could be discriminated from iCCA with high sensitivity (88.6%) and high specificity (88.0%). Conclusions We propose that ME1 is a useful diagnostic marker of INT when used in combination with other hepatocytic and cholangiocytic markers.

Integrative analysis of the characteristic of lipid metabolism-related genes for the prognostic prediction of hepatocellular carcinoma

“…Consistent with a previous study, we found that FMO3 suppresses tumor progression by decreasing cell viability, hence it is a protective index [23]. In addition, our analysis revealed that ME1 or ZIC2, which exhibit stem-cell features, correlated with poor prognosis, hence are risk indexes [24,25]. However, these previous studies reported the presence of potential errors and bias in their analyses.…”

The Value of Contrast-Enhanced Magnetic Resonance Imaging Enhancement in the Differential Diagnosis of Hepatocellular Carcinoma and Combined Hepatocellular Cholangiocarinoma

“…Because most of the cases collected in this study were smaller than 5cm in diameter, and cHCC-CC contained both hepatocellular carcinoma and cholangiocarcinoma, there was no significant difference in AFP, HBsAg and HBeAg between them. Most scholars believe that it originated from hepatic progenitor cells though there are different opinions on the origin of cHCC-CC [26] [27].Hepatic progenitor cells are a group of undifferentiated cells with hepatocyte function in normal human liver, which are mainly distributed in the Hering duct of portal vein and bile canaliculi [28].On the other hand, the Hering duct constructs the relationship between the biliary system and the intralobular anatomy and microscopic system of the liver. Once cHCC-CC occurs, it is easy to have multiple lesions.…”

USP19 exacerbates lipogenesis and colorectal carcinogenesis by stabilizing ME1

“…Cytoplasmic-localized malic enzyme 1 (ME1) reversibly catalyzes the NADP + -dependent conversion of malate to pyruvate (Chen et al, 2019b;Jiang et al, 2013;Lu et al, 2018). ME1 is overexpressed in a variety of cancers and promotes the growth of CRC as well as gastric, breast, and liver cancers (Liao et al, 2018;Lu et al, 2018;Mihara et al, 2019;Nakashima et al, 2018). ME1 plays a critical role in the development of spontaneous and azoxymethane (AOM)/dextran sodium sulphate (DSS)-induced CRCs in mice (Fernandes et al, 2018;Shen et al, 2017).…”