NCOA5 low expression correlates with survival in esophageal squamous cell carcinoma.

The nuclear receptor coactivator 5 (NCOA5) was a unique coactivator independent of AF2 that can modulate ERα-mediated transcription. Recent researches have indicated that its downregulation may participate in cancer development and progression. The aims of the present study were to investigate NCOA5 expression in esophageal squamous cell carcinoma (ESCC) and validate its possible influence on patients' prognosis. NCOA5 expression was examined by immunohistochemical staining in 119 ESCC patients' tissues. Ten paired tumor and adjacent normal specimens were examined by Western blot analysis. Statistical analysis was performed to assess its relevance with various clinicopathologic features and its influence on patients' survival. By immunohistochemistry analysis, NCOA5 expression was found to be significantly correlated with differentiation (P = 0.039), T status (P = 0.047) and stage (P = 0.036). Furthermore, we found NCOA5 higher expression in normal tissues than in tumor tissues by Western blot analysis. Univariate analysis showed that poor differentiation (P = 0.035, P = 0.027), lymph node metastasis (P < 0.001, P < 0.001), high T status (P = 0.010, P = 0.012), advanced stage (P < 0.001, P < 0.001) and NCOA5 low expression (P < 0.001, P < 0.001) were significantly correlated with poor prognosis of both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that NCOA5 low expression (P = 0.019, P = 0.047), high T status (P = 0.015, P = 0.012), lymph node metastasis (P = 0.040, P = 0.021) and advanced stage (P = 0.017, P = 0.046) were independent prognostic factors of poor DFS and OS. Our findings suggest that NCOA5 low expression is associated with ESCC progression and is a potential biomarker in predicting poor prognosis. Further studies of NCOA5 may help develop new therapeutic strategies against ESCC.

Expression of THOP1 and its relationship to prognosis in non-small cell lung cancer.

BACKGROUND: The study was designed to detect the expression level of thimet oligopeptidase (THOP1) protein in non-small cell lung cancer (NSCLC) and investigate its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemical staining was used to determine the expression of THOP1 protein in 120 NSCLC specimens and 53 distant normal lung tissues. Quantitative real-time PCR and western blotting were employed to measure the expression of THOP1 in 16 pairs of primary NSCLC and corresponding normal tissues. RESULTS: Analysis of immunohistochemical staining suggested low THOP1 expression was found in 71 (59.2%) of the 120 NSCLC specimens and significantly correlated with positive lymph node metastasis (P = 0.048). However, low THOP1 expression was found in 22 (41.5%) of the 53 normal lung tissues. Chi-square test suggested that the expression of THOP1 was significantly higher in the normal lung tissues than that in the NSCLC specimens (P = 0.032). Real-Time PCR and western blotting showed that NSCLC specimens had decreased THOP1 mRNA and protein expression compared to corresponding normal tissues. Univariate analysis demonstrated that low THOP1 expression significantly predicted decreased 5-year disease-free survival (P = 0.038) and overall survival (P = 0.017). In addition, positive lymph node metastasis (P = 0.025) and advanced TNM stage (P = 0.009) significantly predicted decreased 5-year overall survival. However, multivariate Cox regression analysis showed that only low THOP1 expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival (P = 0.046) and overall survival (P = 0.021). CONCLUSIONS: THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC.

Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway.

BACKGROUND: Pathological angiogenesis plays an essential role in tumor aggressiveness and leads to unfavorable prognosis. The aim of this study is to detect the potential role of Retinoblastoma binding protein 2 (RBP2) in the tumor angiogenesis of non-small cell lung cancer (NSCLC). METHODS: Immunohistochemical staining was used to detect the expression of RBP2, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34. Two pairs of siRNA sequences and pcDNA3-HA-RBP2 were used to down-regulate and up-regulate RBP2 expression in H1975 and SK-MES-1 cells. An endothelial cell tube formation assay, VEGF enzyme-linked immunosorbent assay, real-time PCR and western blotting were performed to detect the potential mechanisms mediated by RBP2 in tumor angiogenesis. RESULTS: Of the 102 stage I NSCLC specimens analyzed, high RBP2 protein expression is closely associated with tumor size (P = 0.030), high HIF-1α expression (P = 0.028), high VEGF expression (P = 0.048), increased tumor angiogenesis (P = 0.033) and poor prognosis (P = 0.037); high MVD was associated with high HIF-1α expression (P = 0.034), high VEGF expression (P = 0.001) and poor prognosis (P = 0.040). Multivariate analysis indicated that RBP2 had an independent influence on the survival of patients with stage I NSCLC (P = 0.044). By modulating the expression of RBP2, our findings suggested that RBP2 protein depletion decreased HUVECs tube formation by down-regulating VEGF in a conditioned medium. RBP2 stimulated the up-regulation of VEGF, which was dependent on HIF-1α, and activated the HIF-1α via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, VEGF increased the activation of Akt regulated by RBP2. CONCLUSIONS: The RBP2 protein may stimulate HIF-1α expression via the activation of the PI3K/Akt signaling pathway under normoxia and then stimulate VEGF expression. These findings indicate that RBP2 may play a critical role in tumor angiogenesis and serve as an attractive therapeutic target against tumor aggressiveness for early-stage NSCLC patients.

GOLPH3, a good prognostic indicator in early-stage NSCLC related to tumor angiogenesis.

BACKGROUND: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. MATERIALS AND METHODS: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. RESULTS: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p<0.001). Expression of GOLPH3 was found to be an independent prognostic factor in early- stage NSCLC patients, those expressing high levels of GOLPH3 exhibiting a substantially lower 5-year overall survival than GOLPH3-negative patients (adjusted HR =1.899, 95% CI: 1.021-3.532, p=0.043). CONCLUSIONS: High expression of the GOLPH3 protein is common in early-stage NSCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. We conclude a possibility of its use as a diagnostic and prognostic marker in early-stage NSCC patients.

SIRT1 expression is associated with lymphangiogenesis, lymphovascular invasion and prognosis in pN0 esophageal squamous cell carcinoma.

BACKGROUND: Sirtuin1 (SIRT1) is an NAD(+)-dependent type III histone deacetylase (HDAC). This research investigated the prevalence of SIRT1 protein expression and its prognostic influence with the aim of validating its potential role in lymphangiogenesis and lymphovascular invasion (LVI) in pN0 esophageal squamous cell carcinoma (ESCC). METHODS: A total of 206 patients were enrolled in this retrospective study. SIRT1 and VEGF-C protein expression was detected by immunohistochemical staining. Peritumoral lymphatic microvessel density (LVD) and LVI were evaluated by immunostaining for D2-40. Statistical analysis was then preformed to investigate the relevance of SIRT1 expression and various clinicopathologic features and to examine the effect of SIRT1 on tumor-induced lymphangiogenesis, LVI and prognosis. RESULTS: SIRT1 positive expression was identified in 95 cases in the nucleus and was significantly correlated with T status (P < 0.001), disease stage (P = 0.001), VEGF-C positive expression (P = 0.015), high LVD (P = 0.013) and positive LVI (P = 0.015). Patients with SIRT1 positive expression, high LVD and positive LVI had a significantly unfavorable 5-year disease free survival (P < 0.001, P = 0.030, and P < 0.001, respectively) and overall survival (P < 0.001, P = 0.017, and P < 0.001, respectively). However, based on multivariate Cox regression analysis, only SIRT1 positive expression and positive LVI were significant independent prognosticators of poor disease-free survival (P = 0.029 and 0.018, respectively) and overall survival (P = 0.045 and 0.031, respectively). CONCLUSIONS: SIRT1 positive expression was significantly associated with tumor progression, lymphangiogenesis, LVI and poor survival in pN0 ESCC patients. Our research shows a utilization of SIRT1 in prognosing poor survival and providing possible target for ESCC patients through inhibiting its lymphangiogenesis activity.