Sustained cell growth and proliferation, one of the hallmarks of cancer, is considered to responsible for cancer-related deaths by disorganizing the balance of growth promotion and growth limitation. Aberrant activation of the Wnt/β-catenin signaling pathway leads to cell proliferation, growth and survival, and promotes the development of various human tumors, including hepatocellular carcinoma. Elucidating the molecular mechanism of this abnormality in hepatocellular carcinoma carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. Herein, we report that the expression of miR-432 was markedly downregulated in hepatocellular carcinoma cell lines and tissues, and upregulation of miR-432 inhibited, whereas downregulation of miR-432 enhanced the proliferation and tumorigenicity of hepatocellular carcinoma cells both in vitro and in vivo. Furthermore, miR-432 directly targeted and suppressed multiple regulators of the Wnt/β-catenin signaling cascade, including LRP6, TRIM29 and Pygo2, which subsequently deactivated Wnt/β-catenin signaling pathway. Finally, miR-432 expression was inversely correlated with three targets in clinical hepatocellular carcinoma samples. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA by suppressing Wnt/β-catenin signaling activation and may represent a therapeutic target for hepatocellular carcinoma.

Wnt/β-catenin signaling pathway plays important roles in human cancer progression. Better understanding the mechanism underlying regulation of Wnt/β-catenin signaling pathway might provide novel therapeutic targets for cancer treatment. miR-610 expression levels in hepatocellular carcinoma (HCC) cell lines, HCC tissues and 76 archived HCC specimens were determined using real-time PCR. Cell viability was measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The level of DNA synthesis was determined by BrdU incorporation assay. Flow cytometry analysis was used to analyze cell cycle progression. The cells proliferation and tumorigenesis were determined by colony formation and anchorage-independent growth assays in vitro, and by xenograft tumors in vivo. Luciferase assay and micro-ribonucleoprotein complex immunoprecipitation assay were used to confirm the association of the targeted mRNAs with miR-610. miR-610 was downregulated in human HCC cells and tissues, and correlated with HCC progression and patient survival. Inhibition of miR-610 promoted, but overexpression of miR-610 reduced, HCC cell proliferation and tumorigenicity both in vitro and in vivo. Furthermore, we found that inhibiting miR-610 activated, but overexpressing miR-610 decreased, the Wnt/β-catenin activity through directly suppressing lipoprotein receptor-related protein 6 (LRP6) and transducin β–like protein 1 (TBL1X). The in vitro analysis was consistent with the inverse correlation detected between miR-610 levels with expression of LRP6 and TBL1X in a cohort of human HCC samples. Our results indicate that miR-610 downregulation plays essential roles in HCC progression and reduced miR-610 is correlated with Wnt/β-catenin signaling pathway.

Background: Because of the poor health conditions of elderly patients (age >65) with very-early-stage and early-stage hepatocellular carcinoma (HCC), primary treatment via hepatic resection (HR), or radiofrequency ablation (RFA) must be considered. However, few studies have examined this issue. Methods: A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0–20, 21–30, 31–35, and 31–50 mm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed. Results: In total, 1912 patients aged >65 and 2,784 patients aged ≤65 were analyzed after propensity score matching (PSM). For patients >65 with tumors ≤20 mm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.47 and p = 0.76, respectively). For patients with tumors measuring 21–30 mm, the HR group had better OS and a trend toward better DSS compared with the RFA group (p = 0.03 and p = 0.09, respectively). For patients with tumors measuring 31–50 mm, the HR group had better OS and DSS compared with the RFA group (p < 0.001 for both). For patients 65), RFA is recommended for tumors ≤20 mm. For patients older than 65 with tumors measuring 21–50 mm and for those younger than 65 with tumors of any size, HR is the better choice.

Purpose: Ferroptosis, as a novel regulated cell death form, has a close interaction with metabolism, which is largely unknown in cancer. In the present study, we conducted a comprehensive analysis of ferroptosis-related metabolic genes to delineate the metabolic signatures induced by ferroptosis and evaluate its prognostic significance in hepatocellular carcinoma (HCC). Methods: The ferroptosis-related metabolic genes (Fer-MRGs) were identified by correlation analyses with transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus. Then, univariate and the least absolute shrinkage and selection operator Cox regression analysis was used to establish a novel risk score model. Univariate and multivariate COX analyses were used to identify independent prognostic factors for overall survival (OS) of HCC, and a nomogram was developed. The Fer-MRGs’ expression was further evaluated by quantitative real-time polymerase chain reaction in HCC. Results: A total of 77 metabolic genes were identified as Fer-MRGs, and 26 were found with prognostic values for OS of HCC. Then, a novel nine-gene (AKR1C3, ATIC, G6PD, GMPS, GNPDA1, IMPDH1, PRIM1, RRM2, and TXNRD1) risk score model was constructed. Survival analyses showed worse OS in high-risk patients both in the training and validation groups. The model was also identified as an independent prognostic factor for HCC, and a prognostic nomogram for OS was further established with superior discriminative capacity and prediction accuracy. Notably, close correlations were also identified between the risk score and the expression of immune checkpoint genes, immune subtypes of tumor, and susceptibility of HCC to chemotherapeutic agents. Finally, elevated expression of eight Fer-MRGs (except for IMPDH1) was further verified in 16 pairs of HCC tumor and adjacent tissues. Conclusion: These results indicated the intense interaction between ferroptosis and metabolism, the significant role of ferroptosis-related MRGs, and the great potential of the novel risk score model for prognosis prediction in HCC.

Background: The albumin-bilirubin (ALBI) grade is an index that could objectively evaluate liver function. The purpose of this study was to evaluate the prognostic value of postoperative ALBI (post-ALBI) grade and ALBI changes (△ALBI) after hepatectomy in patients with hepatocellular carcinoma (HCC). Methods: The clinical and pathological data of 300 patients with HCC who underwent hepatectomy in the Third Affiliated Hospital of Sun Yat-Sen University from January 19, 2009 to December 25, 2014, were analyzed retrospectively. According to the test data, the patients were divided into post-ALBI grade I, post-ALBI grade II, and post-ALBI grade III groups. According to the receiver operating characteristic curves (ROC), the patients were divided into △ALBI (△ALBI >0.71) high and low groups (△ALBI ≤0.71). Baseline clinical data, recurrence-free survival (RFS) and overall survival (OS) rates were compared between the groups. Results: The 1-, 3-, and 5-year RFS rates and OS rates of patients with post-ALBI grade III were significantly reduced in comparison to those with post-ALBI grade II (P<0.001 both). Between the △ALBI groups, patients with low △ALBI level had significantly reduced 1-, 3-, and 5-year RFS rates and OS rates compared to those with a high △ALBI level (P<0.001 both). Multivariate analyses indicated that higher post-ABLI grade and △ALBI level were significantly independent predictors of an inferior OS and RFS (P<0.05). Conclusions: This study confirmed for the first time that post-ALBI grade and △ALBI could predict the prognosis of patients with HCC after hepatectomy.