RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR). METHODS: HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared between patients with or without splenomegaly, and between patients who did or did not undergo splenectomy for splenomegaly. Propensity score matching (PSM) analysis was performed to match patients in a 1:1 ratio. RESULTS: Of 716 HCC patients with PVTT who underwent LR, 140 patients had splenomegaly (SM group) and 576 patients had no splenomegaly (non-SM group). The SM group was further subdivided into 49 patients who underwent splenectomy (SPT group), and 91 patients who did not received splenectomy (non-SPT group). PSM matched 140 patients in the SM group, and 49 patients in the SPT group. Splenomegaly was an independent risk factor of poor RFS and OS. The OS and RFS rates were significantly better for patients in the non-SM group than the SM group (OS: P<0.001; RFS: P<0.001), and for patients in the SPT group than the non-SPT group (OS: P<0.001; RFS: P<0.001). CONCLUSIONS: Patients who had splenomegaly had significantly worse survival in HCC patients with PVTT. Splenectomy for splenomegaly significantly improved long-term survival in these patients.
RESUMEN
BACKGROUND: Talin-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. METHODS: MHCC-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. RESULTS: Compared 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. CONCLUSION: Both 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.
Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Talina/biosíntesis , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Talina/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. MATERIALS AND METHODS: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell (LO2 cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. RESULTS: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and LO2 cell line (p<0.05). Compared with the LO2 cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). CONCLUSIONS: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.
