Density of tumor infiltrating lymphocytes (TIL) and expressions of certain immune-related genes have prognostic and predictive values in hepatocellular carcinoma (HCC); however, factors determining the immunophenotype of HCC patients are still unclear. In the current study, the transcript sequencing data of liver cancer were systematically analyzed to determine an immune gene marker for the prediction of clinical outcome of HCC.RNASeq data and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), and the samples were assigned into high-stage and low-stage groups. Immune pathway-related genes were screened from the Molecular Signatures Database v4.0 (MsigDB) database. LASSO regression analysis was performed to identify robust immune-related biomarkers in predicting HCC clinical outcomes. Moreover, an immune gene-related prognostic model was established and validated by test sets and Gene Expression Omnibus (GEO) external validation sets.We obtained 319 immune genes from MsigDB, and the genes have different expression profiles in high-stage and low-stage of HCC. Univariate survival analysis found that 17 genes had a significant effect on HCC prognosis, among them, 13 (76.5%) genes were prognostically protective factors. Further lasso regression analysis identified seven potential prognostic markers (IL27, CD1D, NCOA6, CTSE, FCGRT, CFHR1, and APOA2) of robustness, most of which are related to tumor development. Cox regression analysis was further performed to establish a seven immune gene signature, which could stratify the risk of samples in training set, test set and external verification set (p < 0.01), and the AUC in both training set and test set was greater than 0.85, which also greater compared with previous studies.This study constructed a 7-immunogenic marker as novel prognostic markers for predicting survival of HCC patients.
18β-glycyrrhetinic acid (18β-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established.In this study, we investigated the underlying molecular mechanisms of 18β-Gly.Our results showed that 18β-Gly had significant cytotoxic effects and no apparent side effects. 18β-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18β-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-κB) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced.In summary, 18β-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18β-Gly is a novel promising candidate for the treatment of lung cancer.
Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y‐box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. Methods Three bulk and single‐cell RNA‐seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ β ‐catenin pathways. Results YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy‐non‐responsive ICC tissues. The YBX1‐high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness‐related pathways. Moreover, YBX1 expression is significantly correlated with several stemness‐related genes ( SOX9 , OCT4 , CD133 , CD44 and EPCAM ). Additionally, YBX1 overexpression significantly enhanced the colony‐ and spheroid‐forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ β ‐catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ β ‐catenin axis. Conclusions YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ β ‐catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.
Abstract Accumulating evidence has suggested that the ataxia telangiectasia group D complementing ( ATDC ) gene is an emerging cancer‐related gene in multiple human cancer types. However, little is known about the role of ATDC in hepatocellular carcinoma ( HCC ). In this study, we aimed to investigate the expression level, biological function and underlying mechanism of ATDC in HCC . The expression of ATDC in HCC cells was detected by quantitative real‐time polymerase chain reaction and western blot analysis. Cell growth was determined by cell counting kit‐8 assay and colony formation assay. Cell invasion was assessed by Transwell invasion assay. The activation status of Wnt/β‐catenin signalling was evaluated by the luciferase reporter assay. Functional experiments showed that the silencing of ATDC expression significantly suppressed the growth and invasion of HCC cells, whereas the overexpression of ATDC promoted the growth and invasion of HCC cells in vitro. Moreover, we showed that ATDC overexpression promoted the phosphorylation of glycogen synthase kinase ( GSK )‐3β and resulted in the activation of Wnt/β‐catenin signalling. Notably, the inhibition of GSK ‐3β activity significantly abrogated the tumour suppressive effect of ATDC silencing, while the silencing of β‐catenin partially reversed the oncogenic effect of ATDC overexpression. Taken together, these findings reveal an oncogenic role of ATDC in HCC and show that the suppression of ATDC impedes the growth and invasion of HCC cells associated with the inactivation of Wnt/β‐catenin signalling. Our study suggests that ATDC may serve as a potential therapeutic target for HCC .
We previously reported on a novel system termed Lipobead that consists of hydrogel beads encased within an anchored lipid bilayer. The hydrogel particles are formed by inverse suspension polymerization of dimethylacrylamide with N,N'-ethylenebis(acrylamide). During the polymerization stage, the water in oil emulsion is interfacially stabilized by small molecule surfactants as well as a small percentage of lipid functionalized with a vinyl group. The functionalized lipid becomes tethered to the bead surface and promotes the assembly of a lipid bilayer on the surface of the hydrogel beads. The presence of the functionalized lipid during polymerization dramatically alters the yield, average size, and size distribution of beads produced. This paper examines the effect of various chemical and physical processing parameters on the average size and size distribution of beads produced when lipid is a component of the surfactant mixture. Relationships between the processing parameters, average bead size, and size distribution were established. Macroscopic properties of the lipid bilayers of Lipobeads were also evaluated including phase transition temperature as well as permeability to the small polar molecule, adenosine triphosphate. It was established that the presence of functionalized lipid improves the organization of the bilayer on the Lipobead surface.
Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.
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