Identification of cuprotosis-mediated subtypes, the development of a prognosis model, and influence immune microenvironment in hepatocellular carcinoma.

Purpose: Cuprotosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by copper-dependent and associated with mitochondrial respiration. However, the prognostic significance and function of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are unknown. This study aims to develop cuprotosis-mediated patterns-related gene (CMPRG) prediction models for the prognosis of patients with HCC, exploring the functional underlying the CRGs on the influence of tumor microenvironment (TME) features. Experimental design: This study obtained transcriptome profiling and the corresponding clinical information from the TCGA and GEO databases. Besides, the Cox regression model with LASSO was implemented to build a multi-gene signature, which was then validated in an internal validation set and two external validation sets through Kaplan-Meier, DCA, and ROC analyses. Results: According to the LASSO analysis, we screened out a cuprotosis-mediated pattern 5-gene combination (including PBK; MMP1; GNAZ; GPC1 and AKR1D1). A nomogram was constructed for the presentation of the final model. The ROC curve assessed the model's predictive ability, which resulted in an area under the curve (AUC) values ranging from 0.604 to 0.787 underwent internal and two external validation sets. Meanwhile, the risk score divided the patients into two groups of high and low risk, and the survival rate of high-risk patients was significantly lower than that of low-risk patients (P<0.01). The risk score could be an independent prognostic factor in the multifactorial Cox regression analysis (P<0.01). Functional analysis revealed that immune status, mutational loads, and drug sensitivity differed between the two risk groups. Conclusions: In summary, we identified three cuprotosis-mediated patterns in HCC. And CMPRGs are a promising candidate biomarker for HCC early detection, owing to their strong performance in predicting HCC prognosis and therapy. Quantifying cuprotosis-mediated patterns in individual samples may help improve the understanding of multiomic characteristics and guide the development of targeted therapy for HCC.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Silencing of lncRNA EZR-AS1 inhibits proliferation, invasion, and migration of colorectal cancer cells through blocking transforming growth factor ß signaling.

Long non-coding RNA (lncRNA) plays a key regulatory role in the pathogenesis of colorectal cancer (CRC). In the present study, the specific regulatory role of lncRNA ezrin antisense RNA 1 (EZR-AS1) on CRC was investigated. The expression of lncRNA EZR-AS1 was significantly up-regulated in CRC cell lines (HCT8, HCT116, HT29, and SW620 cells), which was significantly different from that of normal human fetal colonic mucosa cells (FHC cells) (P<0.01). HCT116 and HT29 cells were then transfected with EZR-AS1 shRNA (sh-EZR-AS1) to silence lncRNA EZR-AS1 (P<0.01). When compared with the Control, after transfection of SH-EZR-AS1, E-cadherin was up-regulated, Vimentin was down-regulated, the apoptosis rate was increased, the cell viability, wound healing rate, and the number of invasive cells were decreased in HCT116 and HT29 cells (P<0.05). Silencing of lncRNA EZR-AS also significantly reduced the tumor volume and weight in mice injected with sh-EZR-AS1-transfected HCT116 and HT29 cells (P<0.05). The regulatory relationship between lncRNA EZR-AS1 and transforming growth factor ß (TGF-ß) signaling was further identified in CRC cells. Silencing of lncRNA EZR-AS1 significantly down-regulated TGF-ß, Smad2, and α-SMA expression in HCT116 and HT29 cells at the protein level (P<0.05). The intervention of SB431542 (a TGF-ß receptor blocker) and silencing of Smad2 both significantly down-regulated lncRNA EZR-AS1 expression in HCT116 and HT29 cells (P<0.01). In conclusion, silencing of lncRNA EZR-AS1 inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transition, and promoted the apoptosis of CRC cells through blocking TGF-ß signaling.

CircRNA_0000502 promotes hepatocellular carcinoma metastasis and inhibits apoptosis through targeting microRNA-124.

PURPOSE: To investigate the expression level of circ_0000502 in hepatocellular carcinoma (HCC), and to further explore whether it can promote the malignant progression of HCC by targeting and binding to microRNA (miR)-124. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of circ_0000502 in 40 pairs of HCC tissue specimens and adjacent ones, and to analyze the relationship between circ_0000502 expression and prognosis of patients with HCC. QRT-PCR was used to verify the expression of circ_0000502 in HCC cells. The circ_0000502 knockdown model was constructed using lentivirus in HCC cell lines, and cell counting KIT-8 (CCK-8), Transwell and flow cytometry assays were used to figure out the effect of circ_0000502 on the function of HCC cells. Lastly, luciferase reporter gene assay was applied to verify the relationship between circ_0000502 and miR-124. RESULTS: QRT-PCR results indicated that the level of circ_0000502 in HCC tissues was significantly higher than that in adjacent ones. Compared with patients with low expression of circ_0000502, patients with high expression of circ_0000502 had a lower overall survival rate compared with the negative control (NC) group. The proliferation, invasion and migration ability of circ_0000502 knockdown group significantly decreased, while on the contrary cell apoptosis increased. QRT-PCR results revealed that the expression of miR-124 and circ_0000502 mRNA in HCC tissues was negatively correlated. Also, the result of luciferase reporter gene assay demonstrated that circ_0000502 could be targeted by miR-124 via this binding site. CONCLUSIONS: High expression of circ_0000502 was significantly positively correlated with poor prognosis of HCC. Besides, circ_0000502 promoted the malignant progression of HCC by regulating miR-124 expression.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.