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Background: Microvascular invasion (MVI) is recognized as a prognostic factor associated with poor outcome in hepatocellular carcinoma (HCC) patients after curative resection. It remains unclear, however, whether MVI can provide prognostic information for patients at a specific tumor stage.Methods: Consecutive HCC patients who underwent curative resection in years of 2007 and 2008 (discovery cohort) were enrolled in this retrospective study. Patients were stratified by the Barcelona Clinic Liver Cancer (BCLC) staging system. The prognostic significance of MVI for overall survival (OS) and recurrence-free survival (RFS) was studied in each subgroup. The clinical significance of MVI was validated in another cohort of patients underwent curative surgery in the year of 2006 (validation cohort).Results: Of the 1540 patients in the discovery cohort, 389 (25.3%) patients had detectable MVI. Occurrence rates of MVI in the BCLC stage 0, A, and B subgroups were 12.4, 26.2, and 34.4%, respectively. In univariate analysis, MVI was associated with poor OS and RFS (P < 0.001 for both) in HCC patients at stage A, with poor OS in patients at stage 0 (P = 0.028), and with poor RFS at stage B (P = 0.039). In multivariate analysis, MVI was an independent risk factor for OS (HR = 1.431, 95% CI, 1.163-1.761, P < 0.001) and RFS (HR = 1.400, 95% CI, 1.150-1.705, P = 0.001) in patients at stage A; and an independent risk factor for RFS (P = 0.043) in patients at stage B. A similar clinical significance of MVI was found in the validation cohort.Conclusions: MVI has limited prognostic value for HCC patients at BCLC stages 0 and B. For those at stage A, MVI was associated with patient survival and may help to select patients with high risk of disease recurrence. [ABSTRACT FROM AUTHOR]

Background: This study was performed to investigate the role of nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) in regulating hepatocellular carcinoma (HCC) progression. Methods: Expression levels of NLRX1 in clinical specimens and cell lines were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Transwell assays were conducted to evaluate the effect of NLRX1 on cell invasion, and flow cytometry was used to assess apoptosis. Expression patterns of key molecules in the phosphoinositide 3-kinase (PI3K)-AKT pathways were determined via WB. The effect of NLRX1 on cell senescence was evaluated with β-galactosidase assays. Kaplan-Meier analyses and Cox regression models were used for prognostic evaluation. Results: NLRX1 was downregulated in tumor tissue compared with adjacent normal liver tissue. Low tumor NLRX1 expression was identified as an independent indicator for HCC prognosis (recurrence: hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26–2.76, overall survival [OS] 2.26, 95% CI 1.44–3.56). NLRX1 over-expression (OE) significantly inhibited invasiveness ability and induced apoptosis in HCC cells. In vivo experiments showed that NLRX1 knock-down (KD) significantly promoted HCC growth. Mechanistically, NLRX1 exhibited a suppressor function by decreasing phosphorylation of AKT and thus downregulating Snail1 expression, which inhibited epithelial-mesenchymal-transition (EMT) in HCC cells. Moreover, NLRX1 OE could induce cell senescence via an AKT-P21-dependent manner. Conclusions: NLRX1 acted as a tumor suppressor in HCC by inducing apoptosis, promoting senescence, and decreasing invasiveness by repressing PI3K-AKT signaling pathway. Future investigations will focus on restoring expression of NLRX1 to provide new insights into HCC treatment. [ABSTRACT FROM AUTHOR]