Tenofovir vs Entecavir Among Patients With HBV-Related HCC After Resection.

Importance: Tenofovir disoproxil and entecavir are both commonly used first-line antiviral treatments, but their comparative recurrence and overall survival (OS) benefits remain unclear. Objective: To explore differences of tenofovir disoproxil vs entecavir in recurrence-free survival (RFS) and OS after liver resection with curative intent in patients with hepatocellular cancer (HCC) related to hepatitis B virus (HBV). Design, Setting, and Participants: This retrospective cohort study was conducted at Eastern Hepatobiliary Surgery Hospital, a tertiary referral hospital in Shanghai, China, between January 4, 2015, and April 1, 2023. Participants included patients with HBV-related HCC who underwent liver resection with curative intent from January 2015 to December 2018. Patients who received tenofovir disoproxil were matched with patients who received entecavir in a 1:1 ratio using propensity score matching. Data were analyzed from April 3 to May 31, 2023. Exposures: Receiving tenofovir disoproxil or entecavir as antiviral treatment for HBV. Main Outcomes and Measures: Primary end points were RFS and OS rates. Results: Among 4451 patients (mean [SD] age, 58.1 [10.0] years; 3764 male [84.6%]; median [range] follow-up, of 51 [3 to 91] months), 989 patients in each of the groups were selected in propensity score matching. Baseline characteristics were comparable. In propensity score-matched groups, OS rates were 92.2% at 1 year, 70.9% at 3 years, and 54.2% at 5 years in the entecavir group, compared with 90.9% at 1 year, 75.2% at 3 years, and 64.0% at 5 years in the tenofovir disoproxil group. RFS rates were 83.9% at 1 year, 50.0% at 3 years, and 43.3% at 5 years in the entecavir group, compared with 85.3% at 1 year, 55.6% at 3 years, and 51.4% at 5 years in the tenofovir disoproxil group. Patients in the tenofovir disoproxil group had better OS (hazard ratio, 0.82; 95% CI, 0.72 to 0.94; P = .004) and RFS rates (hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) compared with the entecavir group. Restricted mean survival time differences of entecavir vs tenofovir disoproxil groups were -0.05 (95% CI, -0.18 to 0.08) months at 1 year (P = .45), 0.20 (95% CI, -0.62 to 1.03) months at 3 years (P = .63), and 1.82 (95% CI, 0.14 to 3.51) months at 5 years (P = .03). Conclusions and Relevance: These findings suggest that in patients undergoing curative liver resection for HBV-related HCC, tenofovir disoproxil was associated with better long-term OS and RFS rates compared with entecavir, providing insights for antiviral treatment.

LncRNA CCAT1 Upregulates ATG5 to Enhance Autophagy and Promote Gastric Cancer Development by Absorbing miR-140-3p.

BACKGROUND: Long noncoding RNA colon cancer-associated transcript 1 (LncRNA CCAT1) is highly expressed in gastric cancer tissues and plays a role in autophagy. However, the underlying mechanism still needs to be further clarified. OBJECTIVE: To study the role of LncRNA CCAT1 in regulating autophagy of gastric cancer cells, analyze its downstream targets, and elucidate the mechanism. METHODS: qPCR detected the expression of LncRNA CCAT1 in gastric cancer cells. The proliferation, migration, and invasion ability of LncRNA CCAT1 and the expression level of autophagy-related proteins in gastric cancer cells were detected. Bioinformatics method predicted the downstream targets of LncRNA CCAT1, and they were verified by dual-luciferase assay. The relationship between LncRNA CCAT1, miR-140, and ATG5 was verified by co-transfection, and the expression levels of ATG5 and ATG5-ATG12 complex proteins were detected. Finally, the role of LncRNA CCAT1 in vivo was confirmed by gastric cancer transplantation model. RESULTS: LncRNA CCAT1 was highly expressed in gastric cancer cells. LncRNA CCAT1 can promote the proliferation, migration, invasion, and autophagy activity of gastric cancer cells. LncRNA CCAT1 can bind to miR-140-3p and regulate its expression, while miR-140-3p further regulates the expression of ATG5. Overexpression of LncRNA CCAT1 can promote tumor growth in nude mice. After LncRNA CCAT1 silencing, the positive expression rate of ATG5 in nude mice was low. CONCLUSION: LncRNA CCAT1 may inhibit the expression of miR-140-3p by sponge adsorption, thus weakening its inhibitory effect on ATG5. Eventually, gastric cancer cells were more prone to autophagy under the pressure of stress.

Stabilization of snail maintains the sorafenib resistance of hepatocellular carcinoma cells.

Drug resistance is one of the major challenges for treatment of hepatocellular carcinoma (HCC) with sorafenib. Our present study found that sorafenib resistant (SR) HCC cells showed epithelial-mesenchymal transition (EMT) characteristics with the downregulation of epithelial marker and upregulation of mesenchymal makers. The expression of Snail, a core factor of EMT, was increased in HCC/SR cells, while knockdown of Snail can restore sorafenib sensitivity and EMT potential of HCC/SR cells. Further, the upregulation of protein stability was responsible for the upregulation of Snail in HCC/SR cells. ATM and CSN2, which can stabilize Snail protein, were increased in HCC/SR cells. Knockdown of ATM and CSN2 can suppress the expression of Snail and increase sorafenib sensitivity of HCC/SR cells. It indicated that targeted inhibition of Snail might be helpful to overcome sorafenib resistance of HCC patients.