Background. The prediction of hepatocellular carcinoma (HCC) survival is challenging because of its rapid progression. In recent years, necroptosis was found to be involved in the progression of multiple cancer types. However, the role of necroptosis in HCC remains unclear. Methods. Clinicopathological parameters and transcriptomic data of 370 HCC patients were obtained from TCGA-LIHC dataset. Prognosis-related necroptosis genes (PRNGs) were identified and utilized to construct a LASSO risk model. The GEO cohorts (GSE54236 and GSE14520) were used for external validation. We evaluated the distribution of HCC patients, the difference in prognosis, and the accuracy of the prognostic prediction of the LASSO risk model. The immune microenvironment and functional enrichment of different risk groups were further clarified. Finally, we performed a drug sensitivity analysis on the PRNGs that constructed the LASSO model and verified their mRNA expression levels in vitro. Results: A total of 48 differentially expressed genes were identified, 23 of which were PRNGs. We constructed the LASSO risk model using nine genes: SQSTM1, FLT3, HAT1, PLK1, MYCN, KLF9, HSP90AA1, TARDBP, and TNFRSF21. The outcomes of low-risk patients were considerably better than those of high-risk patients in both the training and validation cohorts. In addition, stronger bile acid metabolism, xenobiotic metabolism, and more active immune cells and immune functions were observed in low-risk patients, and high expressions of TARDBP, PLK1, and FLT3 were associated with greater drug sensitivity. With the exception of FLT3, the mRNA expression of the other eight genes was verified in Huh7 and 97H cells. Conclusions. The PRNG signature provides a novel and effective method for predicting the outcome of HCC as well as potential targets for further research.
In recent years, the incidence of esophagogastric junction cancer has increased year by year. It is a special type of gastric cancer, with 80% of patients being clinically in the middle and late stages. The traditional treatment methods are extremely ineffective, and the accuracy of preoperative staging is not good enough. At present, the medical treatment for esophagogastric junction cancer mainly adopts surgery and postoperative adjuvant therapy. The current mainstream clinical diagnostic methods of esophagogastric junction cancer before concurrent neoadjuvant chemoradiotherapy are X-ray, CT examination, and gastroscopic diagnosis. However, these clinical diagnostic methods have many limitations. Endoscopic ultrasonography (EUS) can accurately locate malignant tumors in the digestive tract, surrounding microstructures. It can diagnose lymphatic metastasis so as to provide a clear imaging basis for neoadjuvant chemoradiotherapy. This method can also effectively improve the prognosis of the esophagus and stomach according to the characteristics of the patient. In this experiment, we conducted a controlled trial on patients with stage III esophagogastric junction cancer, divided into an experimental group (neoadjuvant chemotherapy + surgery) and a control group (conventional surgery). The preoperative EUS staging in the control group, the preoperative EUS staging in the neoadjuvant chemoradiotherapy group, and the postoperative pathological staging were compared. The experiment showed that in the control group, the preoperative and postoperative accuracy of EUS was 89.2%, while the preoperative and postoperative accuracy of CT examination was only 62.5%. In the experimental group, the preoperative and postoperative accuracies of EUS and CT were 79.6% and 56.7%, respectively. EUS has both specificity and accuracy due to CT examination. Through studying EUS technology in the staging and diagnosis of esophagogastric junction cancer, the therapeutic effect of esophagogastric junction cancer can be improved. The prognosis of esophagogastric junction cancer can also be improved.
Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn. and has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and five cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, H1975) were evaluated for in vitro cytotoxic activity. Among these, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3-methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the best potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays also showed that compound 8 could better inhibit the migration and invasion of MDA-MB-231 cells, and western blotting assays showed that it could reduce protein expression of HIF-1α, MMP-2 and MMP-9. In addition, flow cytometry assays showed that compound 8 could induce apoptosis in MDA-MB-231 cells by up-regulation of Bax and down-regulation of Bcl-2 and Akt expression.
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