Background Patients undergoing surgical resection of hepatocellular carcinoma (HCC) are at risk of recurrence; however, the underlying mechanism remains poorly understood. Methods Through the analysis of gene expression profiles in tumour and matched normal tissues from patients with hepatocellular carcinoma (HCC), we identified differences in interleukin-11 ( IL-11 ) expression. Further, we used genetic mouse, orthotopic tumour, chemically induced, and orthotopic allograft models to study the correlation between IL-11 and postsurgical recurrence. Additionally, we conducted a series of experiments, including histology and immunohistochemistry analysis, three-dimensional culture, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to investigate the role of IL-11-signal transducer and activator of transcription 3 (STAT3) signaling in HCC recurrence. Findings We demonstrate that IL-11 levels increase after surgery, triggering HCC outgrowth. Accordingly, pharmacological blocking of IL-11-STAT3 signaling in model systems significantly alleviates tumour cell proliferation and suppresses postsurgical recurrence of HCC tumours. Interpretation These data demonstrate that IL-11 has a central role in postsurgical HCC recurrence, and that inhibition of IL-11-STAT3 signaling is a potential therapeutic strategy to prevent recurrence. Fund Natural Science Foundation of China.

BackgroundTalin-1 (TLN-1) and TLN-2 are implicated in many cellular processes, but their roles in hepatocellular carcinoma (HCC) remain unclear. This study aimed to assess cell cycle distribution, anoikis, invasion and migration in human HCC MHCC-97 L cells.MethodsMHCC-97 L cells, which highly express TLN-1, were transduced with TLN-1 shRNA (experimental group) or scramble shRNA (negative control group); non-transduced MHCC-97 L cells were used as blank controls. TLN-1 and TLN-2 mRNA and protein levels were detected by real-time RT-PCR and western blot, respectively. Then, cell cycle distribution and anoikis were assessed by flow cytometry. In addition, migration and invasion abilities were assessed using Transwell and cell scratch assays. Finally, a xenograft nude mouse model was established to further assess cell tumorigenicity.ResultsCompared with the blank and negative control groups, TLN-1/2 mRNA and protein levels were significantly reduced in the experiment group. TLN-1/2 knockdown cells showed significantly more cells in the G0/G1 phase (79.24 %) in comparison with both blank (65.36 %) and negative (62.69 %) control groups; conversely, less cells were found in G2/M and S phases in the experimental group compared with controls. Moreover, anoikis was enhanced (P < 0.05), while invasion and migration abilities were reduced (P < 0.05) in TLN-1/2 knockdown cells compared with controls. TLN-1/2 knockdown inhibited MHCC-97 L cell migration (Percentage of wound healing area: experimental group: 32.6 ± 0.7 % vs. negative controls: 50.1 ± 0.6 % and blank controls: 53.6 ± 0.6 %, both P < 0.01). Finally, the tumors obtained with TLN-1/2 knockdown cells were smaller (P < 0.05) compared with controls.ConclusionBoth TLN-1 and TLN-2 levels correlate with tumorigenicity in human HCC, indicating that these molecules constitute important molecular targets for the diagnosis and/or treatment of HCC.

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Background. The long-term prognosis after curative therapy for hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) remains unsatisfactory due to the high incidence of recurrence. The effect of treatment with nucleotide analogues (NAs) in patients with HBV-related HCC after curative therapy remains unclear. Objective. To assess the impact of using NAs after curative therapy. Method. A computerized literature search was performed; eligible studies were identified from databases. The pooled risk ratios (RRs) and 95% CIs were calculated using Review Manager 5.3. Result. The meta-analysis included a total of 15 studies with 8060 patients. The one-year and three-year recurrence (one-year recurrence: RR 0.41 [95% CI 0.28 to 0.61]; P < 0.00001; three-year recurrence: RR 0.63 [95% CI 0.43 to 0.94]; P = 0.001) and the one-, three-, and five-year overall survival (OS) and disease-free survival (DFS) were significantly better in the treatment group. Conclusion. NAs can reduce the recurrence and improve the prognosis of HBV-related HCC after curative therapy.

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