To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, Po0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (Po0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF (adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary "baited"-global cluster analysis of gene expression profiles. Primary cluster analysis focused on mRNAs encoding matrix proteins and modulators of matrix turnover as classified by Onto-Compare and Gene Ontology and identified both molecules and pathways already implicated in the pathogenesis of TIF (e.g. transforming growth factor ␤1-CTGF-fibronectin-1 pathway) and novel TIF-associated genes (e.g. SPARC and Matrilin-2). Specific gene expression patterns identified by primary extracellular matrix-focused cluster analysis were then used as bioinformatic bait in secondary global clustering, with which to search the renal transcriptome for novel modulators of TIF. Among the genes clustering with ECM proteins in the latter analysis were endoglin, clusterin, and gelsolin. In several notable cases (e.g. claudin-1 and meprin-1␤) the pattern of gene expression identified in adriamycin nephropathy in vivo was replicated during transdifferentiation of renal tubule epithelial cells to a fibroblast-like phenotype in vitro on exposure to transforming growth factor-␤ and epidermal growth factor suggesting a role in fibrogenesis. The further exploration of these complex gene networks should shed light on the core molecular pathways that underpin TIF in renal disease.

Risk characterisation of dietary exposure of aflatoxins (AFs), fumonisins (FBs), deoxynivalenol (DON), zearalenone (ZEA) in maize from Shandong Province was conducted in this study. A total of 520 maize samples were collected after harvesting in 2014 and 2015 from 26 selected villages in Shandong Province, China. A deterministic approach was used in the current study. The dietary intake data of maize was obtained from ‘Shandong Statistical Yearbook 2018’. The risk characterisation of FBs, DON, and ZEA was evaluated in 4 population groups (2 to 6-year-old children, standard adults, city adults and village adults) based on probable intake. 2 to 6-year-old children and adults were exposed to FBs (0.42 and 0.20 μg/kg body weight (bw)/day), DON (0.04 and 0.019 μg/kg bw/day), and ZEA (0.0024 and 0.0011 μg/kg bw/day) through mean maize consumption in diets, which was lower than the provisional maximum tolerable daily intake of each mycotoxin established by JECFA. Risk assessments showed a low risk for liver cancer due to consumption of aflatoxin B1 (0.027-0.21 cases per 100,000 persons per year) contaminated maize compared with China’s current liver cancer incidence of 24.6 cases per 100,000 persons per year.

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