Dataset Information

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

ABSTRACT:

Background & aims

The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers.

Methods

We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 ?m/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed.

Results

There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02).

Conclusions

Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

SUBMITTER: Yasui Y

PROVIDER: S-EPMC4851385 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

Yasui Yutaka Y Abe Tokiya T Kurosaki Masayuki M Higuchi Mayu M Komiyama Yasuyuki Y Yoshida Tsubasa T Hayashi Tsuguru T Kuwabara Konomi K Takaura Kenta K Nakakuki Natsuko N Takada Hitomi H Tamaki Nobuharu N Suzuki Shoko S Nakanishi Hiroyuki H Tsuchiya Kaoru K Itakura Jun J Takahashi Yuka Y Hashiguchi Akinori A Sakamoto Michiie M Izumi Namiki N

PloS one 20160429 4

<h4>Background & aims</h4>The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers.<h4>Methods</h4>We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elast ...[more]

PMID: 27128435

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Project description:Hepatocellular carcinoma (HCC), the most malignant form of primary liver cancer, is the fourth most prevalent cause of cancer mortality globally. It was recently discovered that the dietary fermentable fiber, inulin, can reprogram the murine liver to favor HCC development in a gut microbiota-dependent manner. Determining the molecular pathways that are either over expressed or repressed during inulin-induced HCC would provide a platform of potential therapeutic targets. In the present study, we have combined analysis of the novel inulin-induced HCC murine model and human HCC samples to identify differentially expressed genes (DEGs) in hepatocarcinogenesis. Hepatic transcriptome profiling revealed that there were 674 DEGs in HCC mice compared to mice safeguarded from HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis uncovered enrichment in ECM-receptor interaction, steroid hormone biosynthesis, PPAR signaling pathway, focal adhesion and protein digestion and absorption during inulin-induced HCC. Tandem mass tag based quantitative, multiplexed proteomic analysis delineated 57 differentially expressed proteins, where the over-expressed proteins were associated with cell adhesion molecules, valine, leucine and isoleucine degradation and ECM-receptor interaction. After obtaining the human orthologs of the mouse genes, we did a comparison analysis to level 3 RNA-seq data found in the Cancer Genome Atlas (TCGA) database, corresponding to human HCC (n = 361) and healthy liver (n = 50) samples. Out of the 549 up-regulated and 68 down-regulated human orthologs identified, 142 genes (137 significantly over-expressed and 5 significantly under-expressed) were associated with human HCC. Using univariate survival analysis, we found 27 over-expressed genes involved in cell-cell adhesion and cell division that were associated with poor HCC patient survival. Overall, the genetic and proteomics signatures highlight potential underlying mechanisms in inulin-induced HCC and support that this murine HCC model is human relevant.

Dataset Information

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

Background & aims

Methods

Results

Conclusions

Publications

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

Similar Datasets

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