iu L

Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma

High mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. The expression of HMGB1 has been described in many types of cancers, but the role of HMGB1 in nasopharyngeal carcinoma (NPC) is unknown. The aim of this study was to analyse the roles of HMGB1 in NPC progression and clinical outcome using NPC clinical samples. In an immunohistochemical study, HMGB1 had high expression in 89 of 166 cases of NPC (53.6%). HMGB1 overexpression was significantly associated with T classification (p = 0.01), N classification (p = 0.003), distant metastasis (p = 0.046), and clinical stage (p < 0.001). Patients with higher levels of HMGB1 expression had poorer overall survival and disease‐free survival, whereas patients with lower levels of HMGB1 expression had better survival. Multivariate analysis showed that HMGB1 expression was an independent prognostic indicator for patient survival. Disruption of endogenous HMGB1 using small interfering RNAs suppressed NPC cell invasive ability. These data support the notion that HMGB1 overexpression has a role in the progression of NPC and hence its poor clinical outcome. Copyright

Tiam1 is associated with hepatocellular carcinoma metastasis

We have previously demonstrated that overexpression of T lymphoma invasion and metastasis 1 (Tiam1) is correlated with poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we tried to further investigate the potential roles of Tiam1 in the progression of HCC in a larger set of samples. By detecting Tiam1 expression in 213 HCC patients, we observed that Tiam1 had a higher probability of being overexpressed in HCC patients with metastasis than those without metastasis (68.3% vs. 52.7%, p = 0.036). In addition, the cell line with high metastatic potential expressed more Tiam1 than did the cell line with low metastatic potential. Overexpression of Tiam1 was suggested to be significantly correlated with HCC metastasis. We stably upregulated Tiam1 expression in MHCC97L as well as knocked down Tiam1 expression in HCCLM6. We also investigated the effects of Tiam1 overexpression and knockdown on HCC cells proliferation, migration and invasion in vitro and on tumorigenicity and metastasis in vivo. Overexpression of Tiam1 increased proliferation, migration and invasion of MHCC97L cells, while knockdown of Tiam1 in HCCLM6 cells resulted in the reverse. In vivo functional studies showed upregulation of Tiam1 expression led to an enhancement of tumorigenicity and metastatic potential in mice. However, knockdown of Tiam1 expression exhibited nearly 2.2‐fold retardation in tumor growth and great inhibition on tumor metastases. Our results indicate that Tiam1, as a metastasis‐related gene, may contribute to HCC invasion and metastasis, and consequently, it may be a useful biomarker for therapeutic strategy and control in HCC treatment.

Fascin1 expression predicts poor prognosis in patients with nasopharyngeal carcinoma and correlates with tumor invasion.

BACKGROUND The purpose of this study was to investigate prognostic significance of fascin1 in nasopharyngeal carcinoma (NPC) and evaluate the association of fascin1 with tumor invasion. MATERIALS AND METHODS Immunohistochemical staining for fascin1 was carried out on paraffin-embedded tissue sections from 161 patients with NPC. Data were subjected to statistical analysis with respect to clinicopathological variables and survival. Small interfering RNA (siRNA) approach was used to knockdown fascin1 expression in NPC cells to determine whether fascin1 contributes to tumor cell invasion. RESULTS Immunohistochemical analysis showed that fascin1 was highly expressed in 95 (59.0%) of 161 paraffin-embedded NPC tissues. Fascin1 expression was significantly correlated with clinical stage (P < 0.001) and N classification (P < 0.001). Statistical analysis showed that fascin1 expression was inversely correlated with both overall and disease-free survival of NPC patients. Multivariate analysis showed that fascin1 expression was an independent prognostic indicator for patients survival. Moreover, disruption of endogenous fascin1 expression in NPC cells using siRNA technique suppressed NPC cell invasiveness and decreased cell filopodia and lamellopodia. CONCLUSION The present study indicates that fascin1 expression is inversely correlated with NPC patient survival and directly correlated with the malignant status of NPC.