Aims: To investigate the expression and potential mechanism of action of miR-146b-5p in prostate cancer (PCa).
Methods: Quantification of miR-146b-5p and FOXO3 expression by RT-qPCR was performed on 140 paired PCa and normal adjacent tissues. Kaplan-Meier curves and Cox regression models were used to analyze the relationship between miR-146b-5p expression and 5-year survival outcomes. In vitro experiments were performed in PC-3 and 22RV1 cells to explore the regulatory relationship between miR-146b-5p and FOXO3.
Results: miR-146b-5p is markedly upregulated in PCa tissues and cell lines, exhibiting a significant correlation with tumor stage, Gleason score, lymph node metastasis, and unfavorable prognosis. miR-146b-5p overexpression promoted PCa cell proliferation, migration, and invasion, while inhibition exerted opposite effects. Bioinformatics prediction and dual-luciferase assay confirmed that miR-146b-5p directly targeted the 3'UTR of FOXO3, negatively regulating its expression. Rescue experiments demonstrated that silencing FOXO3 reversed the inhibitory effects of miR-146b-5p inhibitor on PCa cell malignancy.
Conclusions: miR-146b-5p drives PCa progression through the targeted downregulation of FOXO3, implicating it as a promising prognostic marker and therapeutic target.
Background: Transarterial chemoembolization (TACE) is a primary treatment for hepatocellular carcinoma (HCC). Despite its benefits, not all patients experience prolonged survival. Hence, this study aimed to develop a prognostic model using data from HCC patients who underwent TACE.
Methods: This study collected patients with hepatocellular carcinoma who received TACE treatment in the Second Hospital of Dalian Medical University from September 2014 to September 2024 and randomly divided them into the training set and the validation set in a 7:3 ratio. Meanwhile, the data of patients who received TACE treatment at Zhongshan Hospital Affiliated to Dalian University from September 2021 to September 2024 were collected for external validation. Univariable and multivariable Cox analyses in the training cohort identified independent risk factors. Based on these factors, two predictive models were established via Cox regression and random survival forest (RSF). The predictive accuracy of models was appraised using the concordance index (C-index) and the area under the receiver operating characteristic curve (AUC). The calibration of models was assessed via calibration curves.
Results: This study collected clinical data from 815 HCC patients receiving TACE. Independent risk factors included tumor size, TNM stage, serum alpha-fetoprotein, TACE therapy count, and post-treatment direct bilirubin, lactate dehydrogenase, and gamma-glutamyl transferase levels. In the RSF model, AUCs for predicting 1-, 3-, and 5-year OS 0.88 (95% CI: 0.81-0.94), 0.80 (95% CI: 0.74-0.86), and 0.75 (95% CI: 0.67-0.81) in the internal validation cohort, and 0.87(95%CI:0.76,0.98), 0.91(95%CI:0.85,0.97) and 0.89(95%CI:0.82,0.96) in the external validation cohort. The Cox regression model yielded AUCs for OS at 1, 3, and 5 years of 0.92 (95% CI: 0.87-0.96), 0.83 (95% CI: 0.76-0.89), and 0.81 (95% CI: 0.74-0.88) in the internal validation cohort, and 0.86(95%CI:0.75,0.97), 0.89(95%CI:0.82,0.96)and 0.90(95%CI:0.81,0.99) in the external validation cohort. Given its superior AUC and C-index, a more interpretable survival nomogram was built using the Cox model.
Conclusions: The prognostic nomogram, constructed based on routine, interpretable clinical features in this study, may help estimate the risk of death in TACE-treated HCC patients. This tool may provide a crucial reference for decision-making in follow-up treatment and rehabilitation.
Trial registration: Not applicable.
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