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Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

ABSTRACT: Hepatocellular carcinoma develops in either chronically injured or seemingly intact livers. To explore the tumorigenic mechanisms underlying these different conditions, we compared the mRNA expression profiles of mouse hepatocellular tumors induced by the repeated injection of CCl4 or a single diethylnitrosamine (DEN) injection using a cDNA microarray. We identified tumor-associated genes that were expressed differentially in the cirrhotic CCl4 model (H19, Igf2, Cbr3, and Krt20) and the non-cirrhotic DEN model (Tff3, Akr1c18, Gpc3, Afp, and Abcd2) as well as genes that were expressed comparably in both models (Ly6d, Slpi, Spink3, Scd2, and Cpe). The levels and patterns of mRNA expression of these genes were validated by quantitative RT-PCR analyses. Most of these genes were highly expressed in mouse livers during the fetal/neonatal periods. We also examined the mRNA expression of these genes in mouse tumors induced by thioacetamide, another cirrhotic inducer, and those that developed spontaneously in non-cirrhotic livers and found that they shared a similar expression profile as that observed in CCl4 -induced and DEN-induced tumors, respectively. There was a close relationship between the expression levels of Igf2 and H19 mRNA, which were activated in the cirrhotic models. Our results show that mouse liver tumors reactivate fetal/neonatal genes, some of which are specific to cirrhotic or non-cirrhotic modes of pathogenesis.

SUBMITTER: Chen X

PROVIDER: S-EPMC4556385 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

Chen Xi X Yamamoto Masahiro M Fujii Kiyonaga K Nagahama Yasuharu Y Ooshio Takako T Xin Bing B Okada Yoko Y Furukawa Hiroyuki H Nishikawa Yuji Y

Cancer science 20150625 8

Hepatocellular carcinoma develops in either chronically injured or seemingly intact livers. To explore the tumorigenic mechanisms underlying these different conditions, we compared the mRNA expression profiles of mouse hepatocellular tumors induced by the repeated injection of CCl4 or a single diethylnitrosamine (DEN) injection using a cDNA microarray. We identified tumor-associated genes that were expressed differentially in the cirrhotic CCl4 model (H19, Igf2, Cbr3, and Krt20) and the non-cirr ...[more]

PMID: 26011625

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Project description:Purpose:To find potentially diagnostic texture analysis (TA) features and to evaluate the diagnostic accuracy of two-dimensional (2D) magnetic resonance (MR) TA for differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver in an exploratory MR-study. Materials and methods:108 non-cirrhotic patients (62 female; 41.5 ± 18.3 years) undergoing preoperative contrast-enhanced MRI were retrospectively included in this multi-center-study. TA including gray-level histogram, co-occurrence and run-length matrix features (total 19 features) was performed by two independent readers. Native fat-saturated-T1w and T2w as well as arterial and portal-venous post contrast-enhanced 2D-image-slices were assessed. Conventional reading was performed by two separate independent readers. Differences in TA features between HCC and benign lesions were investigated using independent sample t-tests. Logistic regression analysis was performed to obtain the optimal number/combination of TA-features and diagnostic accuracy of TA analysis. Sensitivity and specificity of the better performing radiologist were compared to TA analysis. Results:The highest number of significantly differing TA-features (n = 5) was found using the arterial-phase images including one gray-level histogram (skewness, p = 0.018) and four run-length matrix features (all, p < 0.02). The optimal binary logistic regression model for TA-features of the arterial-phase images contained 13 parameters with an accuracy of 84.5% (sensitivity 84.1%, specificity 84.9%) and area-under-the-curve of 0.92 (95%-confidence-interval 0.85-0.98) for diagnosis of HCC. Conventional reading yielded a significantly lower sensitivity (63.6%, p = 0.027) and no significant difference in specificity (94.6%, p = 0.289) at best. Conclusion:2D-TA of MR images is a feasible objective method that may help to distinguish HCC from benign hepatocellular tumors in the non-cirrhotic liver. Most promising results were found in TA features in the arterial phase images.

Dataset Information

Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

Publications

Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

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