Huijun Zhu

FoxQ1 Overexpression Influences Poor Prognosis in Non-Small Cell Lung Cancer, Associates with the Phenomenon of EMT

Background We determined the expression of forkhead box Q1 (FoxQ1), E-cadherin (E-cad), Mucin 1 (MUC1), vimentin (VIM) and S100 calcium binding protein A4 (S100A4), all epithelial-mesenchymal transition (EMT) indicator proteins in non-small cell lung cancer (NSCLC) tissue samples. We also investigated the relationship between these five proteins expression and other clinicopathologic factors in NSCLC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in NSCLCs patients. Methods Quantitative real-time PCR and immunohistochemistry were used to characterize the expression of the FoxQ1 mRNA and protein in NSCLC. Expression of transcripts and translated products for the other four EMT indicator proteins was assessed by immunohistochemistry in the same clinical NSCLC samples. Results FoxQ1 mRNA and protein were up-regulated in NSCLC compared with normal tissues (P = 0.015 and P<0.001, respectively). Expression of FoxQ1 in adenocarcinoma was higher than in squamous cell carcinoma (P = 0.005), and high expression of FoxQ1 correlated with loss of E-cad expression (P = 0.012), and anomalous positivity of VIM (P = 0.024) and S100A4 (P = 0.004). Additional survival analysis showed that high expression of FoxQ1 (P = 0.047) and E-cad (P = 0.021) were independent prognostic factors. Conclusion FoxQ1 maybe plays a specific role in the EMT of NSCLC, and could be used as a prognostic factor for NSCLC.

High expression of FoxP1 is associated with improved survival in patients with non-small cell lung cancer.

FoxP1 has been reported to be expressed in several types of human malignant tumors, and has been associated with metastasis and patient prognosis. Quantitative real-time polymerase chain reaction (PCR) and immunohistochemical analysis with tissue microarray were used to characterize the expression of FoxP1 in non-small cell lung cancer (NSCLC). It was revealed that the expression of FoxP1 messenger RNA (mRNA) and protein was significantly higher in NSCLC tissue than in corresponding peritumoral tissue (P = .013 and P < .001, respectively). The expression of FoxP1 protein in NSCLC was related to gender, histologic type, and 5-year survival rate (all P < .05). Finally, we evaluated the prognostic significance of the expression of FoxP1 in a group of patients. Kaplan-Meier survival and Cox regression analyses showed that low expression of FoxP1 (P < .001) and later stage grouping by TNM (P = .022) were independent factors predicting poor prognosis for NSCLC.

High expression of RAB27A and TP53 in pancreatic cancer predicts poor survival

AbstractRAB27A is a member of Rab family GTPases involved in cellular vesicle trafficking, and TP53 has recently been implicated in regulating the exosome secretion pathway. Because exosome secretion plays an important role in modulating tumor microenvironment and invasive growth, we hypothesized that RAB27A and TP53 expression might be associated with aggressive behavior in pancreatic ductal adenocarcinoma (PDAC), one of the most deadly human malignancies. We determined protein expression of RAB27A and TP53 in 265 pancreatic tissues (186 carcinomas and 79 normal or benign tissues) by immunohistochemistry analysis on tissue microarray and found their expression was correlated with patients’ clinical parameters and overall survival. We found that RAB27A and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. High RAB27A protein expression (RAB27A+) was significantly associated with tumor stage and vascular invasion. No correlation between RAB27A and TP53 expression was observed. Patients with high RAB27A expression and high TP53 expression had a poor overall survival. Our data indicate that RAB27A expression is an independent prognostic marker for PDAC, and RAB27A-regulated exosome secretion pathway may represent a novel therapeutic target in pancreatic cancer .

Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma.

The human trophoblastic cell surface antigen 2 (TROP2) gene is associated with the development of malignancies, but its expression in laryngeal squamous cell carcinoma (SCC) and its relationship with clinical characteristics of the disease remain undetermined.

Over-expression of ROR2 and Wnt5a cooperatively correlates with unfavorable prognosis in patients with non-small cell lung cancer

We investigated the expression of receptor tyrosine kinase-like orphan receptor (ROR) 2 and Wnt5a and their prognostic significance in non-small cell lung cancer (NSCLC). Tissue microarray-based immunohistochemical analysis was performed to determine the expression of ROR2 and Wnt5a in 219 patients. mRNA expression of ROR2 and Wnt5a was examined in 20 pairs of NSCLC and matched adjacent normal tissues by real-time PCR. Compared with non-tumorous tissues, both mRNA expression and protein product of ROR2 and Wnt5a genes were significantly increased in NSCLC. c2 analysis revealed that high ROR2 or Wnt5a expression in NSCLC was significantly associated with advanced TNM stage. High expression of both ROR2 and Wnt5a was also related to advanced TNM stage. Multivariate analyses suggested that ROR2, Wnt5a and TNM stage were independent prognostic factors in NSCLC. Our clinical findings suggest that high ROR2 or Wnt5a expression is associated with poor prognosis in NSCLC, and combined detection of ROR2 and Wnt5a is helpful in predicting the prognosis of NSCLC.

High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma.

RTK-like orphan receptor 2 (ROR2) is overexpressed in several cancers and has tumorigenic activity. However, the expression of ROR2 and its functional and prognostic significance have yet to be evaluated in pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time polymerase chain reaction was used to characterize the expression of ROR2 mRNA in PDAC, corresponding peritumoral tissues, and PDAC cell lines. Immunohistochemical analysis with tissue microarrays was used to evaluate ROR2 expression in PDAC and to investigate the relationship of this expression to clinicopathological factors and prognosis. The expression of ROR2 mRNA and protein was significantly higher in PDAC than in normal pancreatic tissues. High cytoplasmic ROR2 expression in cancer cells was significantly associated with a primary tumor, distant metastasis, and TNM stage, and high stromal ROR2 expression was significantly associated with regional lymph node metastasis and TNM stage. The Kaplan–Meier method and Cox regression analyses showed that high ROR2 expression in tumor cytoplasm or stromal cells was significantly associated with malignant attributes and reduced survival in PDAC. We present strong evidence that ROR2 could be used as an indicator of poor prognosis and could represent a novel therapeutic target for PDAC.

High CD133 Expression in the Nucleus and Cytoplasm Predicts Poor Prognosis in Non-Small Cell Lung Cancer

Objective. The aim of this study was to investigate the expression of Prominin-1 (CD133) in cancer cells and its potential value as a prognostic indicator of survival in patients with non-small cell lung cancer (NSCLC). Methods. Cancerous tissues and matched normal tissues adjacent to the carcinoma from 239 NSCLC patients were obtained immediately after surgery. Immunohistochemistry of tissue microarrays was used to characterize the expression of CD133 in NSCLC and adjacent tissues. The correlation of CD133 expression with clinical characteristics and prognosis was determined by statistical analysis. Results. CD133 protein expression levels in both the cytoplasm and nucleus were significantly higher in NSCLC tissues compared with corresponding peritumoral tissue (P < 0.05). CD133 expression in the nucleus of NSCLC cells was related to tumor diameter (P = 0.027), tumor differentiation (P < 0.001), and TNM stage (P = 0.007). Kaplan-Meier survival and Cox regression analyses revealed that high CD133 expression in the nucleus was an independent predictor of poor prognosis of NSCLC, as was high cytoplasmic CD133 expression (P < 0.001). Conclusion. Our findings provide the first evidence that high expression of CD133 in both the nucleus and cytoplasm is associated with poor prognosis in NSCLC.

The patterns and expression of KDR in normal tissues of human internal organs

KDR has been implicated for playing an important role in the formation of new blood vessels and in solid tumor growth. It was considered as one of the most important regulators of angiogenesis and a key target in anticancer treatment. In the present study, we characterized KDR mRNA and protein expression in normal tissues of perinatal and adult tissues using One-step Real-Time RT-PCR and immunohistochemistry with a self-made anti-KDR antibody. The expression of KDR mRNA and protein in perinatal internal organs were all higher than in adult organs including brain, kidney, liver, lung and heart, respectively. KDR protein was presented in the cell plasma membrane of human internal tissues. The expression of KDR protein was raised in macrophage of spleen, and decreased in neurons of brain, myocardium, bronchial epithelial cells and alveolar epithelial cell, proximal and distal tubules cells, and hepatic cells with the maturity process of human organs. Notably, the order of KDR protein expression from highest to lowest is as follows: brain, liver, heart, kidney, and lung in adult tissues with statistically significant. It follows that how to balance the potential therapeutic side effect with human internal organs in targeted therapy of over-expressing KDR tumor.

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer

Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen (CTA) family, which is one of the largest groups of human tumor-associated antigens. MAGE-A9 is a particular member in the context of the MAGE-A gene family and was defined as presenting prognostic relevance in certain type of human cancer. However, the expression of MAGE-A9 in invasive ductal breast cancer (IDC) and the relationship with the clinical attributes of IDC, especially prognostic characteristic, remain poorly understood. In this present study, one-step quantitative reverse transcription polymerase chain reaction (18 fresh-frozen IDC tissues and corresponding non-cancerous tissues) and immunohistochemistry by tissue microarrays (82 IDC tissue samples and 70 matched tumor-adjacent non-cancerous tissue samples) were performed to characterize expression of the MAGE-A9 gene in IDC. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. The results of qPCR and IHC analysis showed that the expression of MAGE-A9 in IDC was significantly higher than that in corresponding non-cancerous tissue. Moreover, the expression level of MAGE-A9 protein in IDC was significantly related to histological grade (p = 0.011) and distant metastasis (p = 0.019). Multivariate analysis with the Cox regression model showed that MAGE-A9 protein expression (p = 0.009), histological grade (p = 0.014), lymph node metastasis (p = 0.012) and distant metastasis (p = 0.011) were independent prognostic factors for overall survival of IDC patients. The data suggest that MAGE-A9 expression is correlated with malignant attributes of IDC and it may serve as a novel prognostic factor and an ideal candidate for targeted therapy in IDC treatment.

Trop2 is overexpressed in gastric cancer and predicts poor prognosis

The cell surface protein Trop2 is overexpressed in a variety of human cancers. Trop2 expression increases tumor development and metastasis and reduces patient survival. However, little is known about the role of Trop2 expression and its prognostic value in gastric cancer (GC), particularly in Chinese populations. We analyzed Trop2 expression in GC tissues collected from Chinese GC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry on tissue microarrays were performed to assess levels of Trop2 mRNA and protein in GC, and correlations between Trop2 expression and clinical characteristics and prognosis were analyzed. Trop2 expression was higher in GC tissues than in neighboring non-tumor tissues. Increased Trop2 protein levels in GC were associated with increased differentiation, tumor node metastasis stage, tumor size, lymph node metastasis, distant metastasis, and H. pylori infection. GC patients with high Trop2 expression also had poor overall survival rates. These data suggest Trop2 is a useful prognostic biomarker for GC.