Gastric cancer (GC) is a common malignant disease worldwide. Aberrant miRNAs expression contributes to malignant cells behaviour, and in preclinical research, miRNA targeting has shown potential for improving GC therapy. Our present study demonstrated that miR-632 promotes GC progression in a trefoil factor 1 (TFF1)-dependent manner. We collected GC tissues and serum samples to detect miR-632 expression using real-time PCR. A dual-luciferase reporter assay was used to identify whether miR-632 directly regulates TFF1 expression. Tube formation and endothelial cell recruitment assays were performed with or without miR-632 treatment. Western blot and in situ hybridization assays were performed to detect angiogenesis and endothelial recruitment markers that are affected by miR-632. Our results showed that miR-632 is highly expressed in GC tissue and serum and negatively associated with TFF1 in GC. miR-632 improves tube formation and endothelial cell recruitment by negatively regulating TFF1 in GC cells. Recombinant TFF1 reversed miR-632-mediated angiogenesis. TFF1 is a target gene of miR-632. Our study demonstrated that miR-632 promotes GC progression by accelerating angiogenesis in a TFF1-dependent manner. Targeting of miR-632 may be a potential therapeutic approach for GC patients.

Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives.

Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5–14.6) and 3.5 months (95% CI: 2.3–4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility.

The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was −8.6%/month, and patients were divided into two groups according to TGR. Kaplan–Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23–3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13–3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35–0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance.

Purpose: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). This study aimed to construct a novel nomogram model for predicting the risk of HCC in patients with HBV infection. Patients and Methods: This retrospective study analyzed clinical data from healthcare databases in Xiamen, encompassing 5161 adults with HBV infection without HCC and 2819 adults with HBV-related HCC between January 2016 and December 2020. Subsequently, the patients were randomly divided into a training set (n=5586) and testing set (n=2394). The training set was used to identify the risk factors for HCC development and to construct an HCC risk prediction nomogram model. The predictive accuracy of the model was assessed using the receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) in both sets. Furthermore, the performance of the nomogram model was compared with that of the existing models. Results: Multivariate analysis revealed that age, sex, liver cirrhosis, neutrophil/platelet count ratio (NLR), serum bilirubin (TBIL), aspartate aminotransferase (AST), serum albumin (ALB), serum alpha-fetoprotein (AFP), and HBV DNA were independently associated with HCC. A nomogram model was developed by incorporating these risk factors. The the receiver operating characteristic curve (AUC) of the nomogram model were 0.897 and 0.902 for the training and testing sets, respectively. Analysis of the AUC demonstrated that the nomogram model exhibited significantly enhanced predictive performance for HCC compared to the alternative risk scores in both sets. Furthermore, DCA indicated that the nomogram model provided a broad range of threshold probabilities related to the net clinical benefits. A web-based calculator was developed(https://nomogram-model-hcc.shinyapps.io/DynNomapp/). Conclusion: The novel nomogram model, which includes age, sex, liver cirrhosis, NLR, TBIL, AST, ALB, AFP, and HBV DNA as factors, precisely predicts the risk of HCC in patients with chronic hepatitis B(CHB) and outperforms the existing models.

Purpose: To investigate the prognostic value of post-treatment prognostic nutritional index (PNI) in advanced hepatocellular carcinoma (HCC) patients treated with immune‑based therapy, and explore its correlation with nutritional-inflammatory markers and treatment response. Methods: This retrospective study enrolled 133 patients with unresectable or metastatic HCC who received first- or second-line immune-based regimens (February 2019–September 2022). Patients were stratified by median post-treatment PNI (46.3). Survival was analyzed using Kaplan-Meier and Cox regression methods; subgroup interaction, Spearman correlation, and ROC analyses were also performed. Results: Significant baseline differences in Child-Pugh grade, vascular invasion, tumor size, baseline PNI, and median follow-up were observed between groups (all P < 0.05) and adjusted for in multivariate models. Elevated post-treatment PNI independently predicted longer overall survival (median 24.80 vs. 12.27 months, HR = 0.597, 95% CI 0.362– 0.983, P = 0.043) and progression-free survival (median 17.07 vs. 7.47 months, HR = 0.558, 95% CI 0.317– 0.981, P = 0.043). No significant subgroup interaction was observed for PFS (all interaction P > 0.05); for OS, effect modification was suggested for tumor number (interaction P = 0.036) and AFP level (interaction P = 0.035). Post-treatment PNI positively correlated with albumin (r = 0.862) and lymphocyte count (r = 0.632), and negatively with NLR (r = − 0.429) and CRP (r = − 0.354). It showed moderate discriminatory ability for objective response (AUC = 0.663). Dynamic change in PNI (ΔPNI) lacked prognostic significance. Median follow-up was 17.2 months. Conclusion: Post‑treatment PNI is an independent prognostic biomarker in advanced HCC treated with immune‑based therapy, closely reflecting nutritional-inflammatory status and showing moderate discriminatory ability for treatment response. Dynamic PNI changes provided no incremental prognostic value in this cohort.