Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer.

Metastasis is a fatal status for liver cancer, and the identification of an effective prediction model and promising therapeutic target is essential. Given the known relationship between fatty acid (FA) metabolism and the liver, the present study aimed to investigate dysregulation of genes associated with FA metabolism in liver cancer. Bioinformatics analyses were performed on data from patients with hepatocellular carcinoma (HCC) obtained from The Cancer Genome Atlas database using R software packages. Online public tools such as the Human Protein Atlas, Tumor Immune Single-Cell Hub and the University of Alabama at Birmingham Cancer Data Analysis portal were also utilized. Some essential results were further verified using in vitro experiments using HepG2 liver cancer cells. A signature consisting of three genes associated with the progression and prognosis of HCC and FA metabolism was identified. When samples were scored based on the expression of these genes and divided according to the median value, the higher score group showed a worse outcome and repressive immune microenvironment than the lower score group. Downstream pathways such as hypoxia, IL6/JAK/STAT3 and epithelial-mesenchymal transition were found to be significantly activated in the higher score group. As the core factor in the signature, mitochondrial ribosomal protein L35 (MRPL35) was found to be upregulated in HCC and to have certain impacts on the dysregulation of effective immunity. Further investigations and in vitro experiments indicated that MRPL35 facilitates the migration and invasion abilities of liver cancer, and the resistance of HCC to treatment. These findings have important implications regarding the characteristics and mechanisms of metastasis in liver cancer, and provide a promising signature based on FA metabolism-related genes that may be used to predict outcomes and explored as a novel therapeutic target in liver cancer.

Involvement of NF-κB/PI3K/AKT signaling pathway in the protective effect of prunetin against a diethylnitrosamine induced hepatocellular carcinogenesis in rats.

Prunetin (PRU) is an O-methylated flavonoid that is present in various natural plants and a primary significant compound found in isoflavone. Liver cancer creates major carcinogenic death despite recently advanced therapies. Hepatocellular carcinoma (HCC) treatment and prognosis are better in people with secure liver function. In the present study, we evaluated the action of PRU on diethylnitrosamine (DEN) alone HCC in a rat model through inflammation-mediated cell proliferative phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway analysis. Male Wistar rats were divided into four groups of six rats each. Group I, normal rats; Group II, DEN alone; Group III, DEN + PRU, and Group IV, PRU-alone. All groups of rats carried out hepatic cancer development by hypothesis antioxidant, biochemical, cell proliferative, apoptosis, cytokines protein, and gene expression status profiles. In tumor incidence DEN + PRU, 100% delayed the tumor growth disappearance of the lesion,  and reversal of normal liver architecture was observed. Liver marker enzymes levels decreased when antioxidant levels (superoxidase dismutase, catalase, glutathione peroxidase, and glutathione reductase) were in Group III. Proinflammatory markers nuclear factor-κB, interleukin (IL)-6, IL-1ß, and tumor necrosis factor α, were elevated in the rat's serum in Group III. Cell proliferative markers proliferating cell nuclear antigen and Cyclin-D1 protein expressions were downregulated; in contrast, Bcl-2, Bax, caspase-3, and caspase-9 gene expressions were upregulated and then it followed that protein expression of PI3K/AKT was downregulated in PRU-treated groups. PRU assisted reversal of liver damage, antioxidant enzyme restoration cytokine balance, protein, and gene expression to control levels. Taken together, PRU improves functions of the liver, and as such prevents HCC. PRU can be used together with chemopreventives for HCC.

Surgical strategy for isolated caudate lobectomy: experience with 16 cases.

Introduction. Surgical resection is the most effective treatment for neoplasm in the caudate lobe. Isolated caudate lobectomy is still a challenge for hepatobiliary surgeons. No widely accepted surgical strategy for the procedure has been developed yet. Objective. To get a better understanding of isolated caudate lobectomy and to optimize the procedure. Materials and Methods. 16 cases of isolated caudate lobectomy were reviewed to summarize the surgical experience. Results. All the 16 cases of isolated caudate lobectomy were carried out successfully, among which left side approach was adopted in two cases (12.5%), right side approach in three cases (18.75%), and both sides approach in 11 cases (68.75%). No severe complications occurred. Conclusion. The majority of neoplasms confined to the caudate lobe can be resected safely by left and right side approach with proper anatomic surgical procedure, usually in the sequence of mobilization, outflow control, inflow control, and division of the hepatic parenchyma. Fully mobilizing the caudate lobe from the inferior vena cava (IVC) is of great importance. Division of the retrohepatic ligament and the venous ligament facilitated the procedure.