While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction.Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC. K E Y W O R D SGEO, hepatocellular carcinoma, metabolism, prognostic model, TCGA

Never in mitosis gene-A (NIMA)-related expressed kinase 2 (NEK2) has been recently reported to play a role in tumor progression, drug resistance and tumorigenesis. However, little is known about the effects of NEK2 in hepatocellular carcinoma (HCC) metastasis and the underlying mechanism. NEK2 expression levels were examined by immunochemistry, qRT-PCR and western blot analyses in HCC cell lines and HCC tissues. A Transwell assay was used to determine the migration and invasion capacity of NEK2-silenced or NEK2-overexpressing HCC cells. Cell proliferation was investigated by MTT [(3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenytetrazolium bromide] assay. The expression levels of epithelial-mesenchymal transition (EMT) markers in NEK2-silenced or NEK2-overexpressing HCC cells were examined by western blot analyses and qRT-PCR. The correlations between NEK2 expression and clinicopathological characteristics were further analyzed. Gene microarray was further used to analyze the effect of NEK2 expression on downstream cell signals. Our study showed that NEK2 was overexpressed in human HCC (37.84%; 98/259). NEK2 overexpression was significantly associated with liver non-capsulation and predicted poor survival outcomes in HCC patients after hepatectomy. In addition, NEK2 significantly enhanced HCC cell invasive ability. Mechanistically, we found that the epithelial-mesenchymal transition (EMT) plays a pivotal role in the NEK2-mediated promotion of HCC cell invasion. Furthermore, we provided evidence that signaling through the Wnt, NF-κB, focal adhesion, VEGF, Hippo and p53 pathways may be downstream of NEK2. Our findings highlight the importance of NEK2 in HCC metastasis and suggest that NEK2 is a reliable prognostic marker for HCC patients after hepatectomy.

Fructose-1,6-bisphosphatase (FBP1), one of the rate-limiting gluconeogenic enzymes, plays critical roles in several cancers and is treated as a tumour suppressor. However, its role in hepatocellular carcinoma (HCC) is unclear. Here, we demonstrated that FBP1 was significantly inhibited during Snail-induced epithelial to mesenchymal transition (EMT) and tissues in HCC. Restoration of FBP1 expression in HCC cancer cells suppressed EMT phenotype, tumour migration and tumour growth induced by Snail overexpression in SMMC-7721 cells. Gene set enrichment analyses revealed significantly enriched terms, including WNT, Notch, ESC, CSR and PDGF, in the group with high Snail and low FBP1 compared with those with low Snail and high FBP1. Low FBP1 expression was significantly correlated with higher AFP level, satellite nodules, portal vein tumour thrombus, and advanced tumour stage. Survival analyses showed that FBP1 was an independent prognostic factor for overall survival and recurrence-free survival. In conclusion, our study revealed a vital role for FBP1 in Snail-induced EMT and prognostic prediction in HCC.

MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.

Papular elastorrhexis is a rare cutaneous disorder; only 27 cases have been reported before the present review. We added four new cases, and reviewed the published literature in both English and Chinese language. To data, 31 cases have been reported, in the range of 4-40 years (n = 31, median 20 years, mean age 19.5 years). Among them, only a familial cluster was reported, the ratio of male/female was 11:20. The age for the first detection of the lesions was from 3 to 35.5 years (n = 26, median age 14 years, mean age 15.3 years). The duration between the initial detection of the lesion to consultation was from 3 weeks to 20 years (n = 27, median time 1 year, mean time 3.1 years). Of the 26 patients with details, 9 detected their initial lesions in the first decade, 11 in the second decade, 5 in the third decade and only 1 older than 30 years. Twenty out of 31 patients showed nonfollicular papules while the rest had been not mentioned the condition. The lesions may distribute over trunk, limbs, and rarely on shoulders, scalp, face, mandibula, retroauricular region, occipitocervical, neck, armpits, thighs. Histopathological examination shows focal loss or decrease of elastic fibers, that may also appear thin and fragmented. There may be mild perivascular lymphocytic infiltrate in the dermis. The collagen bundles can be thickened and homogenized, or normal. No suggestive therapies were proposed at present.