Fatty acid metabolism is closely linked to the progression of gastric cancer (GC), a very aggressive and life-threatening tumor. This study examines linked molecules, such as Sterol Regulatory Element-Binding Protein 1 (SREBP1), ATP Citrate Lyase (ACLY), Acetyl-CoA Synthases (ACSs), Acetyl-CoA Carboxylase (ACC), Fatty Acid Synthase (FASN), Stearoyl-CoA Desaturase 1 (SCD1), CD36, Fatty Acid Binding Proteins (FABPs), and Carnitine palmitoyltransferase 1 (CPT1), as well as their latest studies and findings in gastric cancer to unveil its core mechanism. The major enzymes of fatty acid de novo synthesis are ACLY, ACSs, ACC, FASN, and SCD1, while SREBP1 is the upstream molecule of fatty acid anabolism. Fatty acid absorption is mediated by CD36 and FABPs, and fatty acid catabolism is mediated by CPT1. If at all possible, we will discover novel links between fatty acid metabolism and a prospective gastric cancer target.

DOK is a new type of regulatory protein family that participates in the regulation of tumor cell growth. However, most of the studies are conducted in cell lines, and systematic studies have not been conducted in human tumors. We conducted a comprehensive analysis of DOK based on its expression profile and its relationship with patient survival, immune infiltration, tumor microenvironment, and drug sensitivity. We used the TCGA database to analyze the correlation between DOK family gene expression and prognosis and clinical stage. The protein expression of DOK in tumor tissues was analyzed by immunohistochemistry. Use the cBioPortal database to analyze the alteration frequency in DOK family genes in human tumors. In addition, we used ESTIMATE algorithm and TIMER website to analyze the correlation between DOK family genes and tumor immunity. Finally, we further analyzed the relationship between DOK family genes and tumor stemness and the sensitivity of cancer cells to chemotherapy. We conducted a comprehensive analysis of DOK family genes based on its expression profile and its relationship with patient survival. We also confirmed this conclusion by immunohistochemistry. The expression of DOK family genes is related to OS, clinical stage, tumor mutation, methylation, CNV, and SNV. DOK family genes are significantly associated with poor prognosis of UVM. DOK1-DOK3 has obvious correlation with tumor immunity. DOK2 can increase the sensitivity of chemotherapy drugs, while DOK4 reduces the sensitivity of multiple chemotherapy drugs. In addition, the expression level of DOK family genes is significantly correlated with the activity of cancer marker-related pathways. DOK plays a role of tumor suppressor gene or tumor-promoting gene in different tumors. However, DOK family genes play a role in promoting cancer in UVM. DOK family genes are significantly associated with drug sensitivity.

Background: Many reports have described that abnormal nectin-4 expression may be used as a prognostic marker in many tumors. However, these studies failed to reach a consensus. Here, we performed a meta-analysis to comprehensively evaluate the prognostic value of nectin-4 in cancers.Methods: Relevant studies were identified through a comprehensive search of PubMed, EMBASE and Web of science until August 31, 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the relationship between nectin-4 expression and overall survival (OS) and disease-free survival/progression-free survival/relapse-free survival (DFS/PFS/RFS). Odds ratios (ORs) with 95% CIs were applied to assess the relationship between nectin-4 expression and clinicopathologic features. Subgroup analysis was performed to explore the sources of heterogeneity. Sensitivity analysis and funnel plot were used to test the reliability of the results. All data analyses were performed using STATA version 12.0 software.Results: Fifteen articles involving 2245 patients were included in the meta-analysis. The pooled analysis showed that high nectin-4 expression was significantly associated with poor OS (HR: 1.75, 95% CI: 1.35–2.28). There was no relationship between high nectin-4 expression and DFS/PFS/RFS (HR: 178, 95% CI: 0.78–4.08).Subgroup analyses revealed that that high nectin-4 expression mainly presented adverse OS in esophageal cancer (EC) (HR: 1.78, 95% CI: 1.30–2.44) and gastric cancer (GC) (HR: 1.92, 95% CI: 1.43–2.58). We also found that high nectin-4 expression was associated with tumor diameter (big vs small) (OR: 1.96, 95% CI: 1.02–3.75), tumor stage (III-IV vs I-II) (OR: 2.04, 95% CI: 1.01–4.12) and invasion depth (T3+T4 vs T2+T1) (OR: 3.95, 95% CI: 2.06–7.57).Conclusions: Nectin-4 can be used as an effective prognostic indicator for specific cancers.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC–MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45–807.43) and 484.22 (311.91–626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Hepatic ischemia-reperfusion injury (HIRI) significantly contributes to liver dysfunction following liver transplantation and hepatectomy. However, the role of the celiac ganglion (CG) in HIRI remains unclear. Adeno-associated virus was used to silence Bmal1 expression in the CG of twelve beagles that were randomly assigned to the Bmal1 knockdown group (KO-Bmal1) and the control group. After four weeks, a canine HIRI model was established, and CG, liver tissue, and serum samples were collected for analysis. The virus significantly downregulated Bmal1 expression in the CG. Immunofluorescence staining confirmed a lower proportion of c-fos⁺ and NGF⁺ neurons in TH⁺ cells in the KO-Bmal1 group than in the control group. The KO-Bmal1 group exhibited lower Suzuki scores and serum ALT and AST levels than the control group. Bmal1 knockdown significantly reduced liver fat reserve, hepatocyte apoptosis, and liver fibrosis, and it increased liver glycogen accumulation. We also observed that Bmal1 downregulation inhibited the hepatic neurotransmitter norepinephrine, neuropeptide Y levels, and sympathetic nerve activity in HIRI. Finally, we confirmed that decreased Bmal1 expression in CG reduces TNF-α, IL-1β, and MDA levels and increases GSH levels in the liver. The downregulation of Bmal1 expression in CG suppresses neural activity and improves hepatocyte injury in the beagle model after HIRI.

[This corrects the article DOI: 10.1155/2021/6485871.].