Jianfei Huang

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 .

Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer.

The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P<0.001 and P=0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ(2) test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P=0.023), P53 status (P=0.042), Cyclin D1 status (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.004) and TNM staging (P<0.001). Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.

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.

Transplantation of RADA16-BDNF peptide scaffold with human umbilical cord mesenchymal stem cells forced with CXCR4 and activated astrocytes for repair of traumatic brain injury.

Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCsCXCR4 and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI. STATEMENT OF SIGNIFICANCE In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application.

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.

Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer

Isocitrate dehydrogenase (IDH1) is an NADP-dependent enzyme that catalyzes the decarboxylation of isocitrate to alpha-ketoglutarate. The IDH1-R132H mutation predicts a better clinical outcome for glioma patients, and the expression of IDH1-R132H correlates with a favorable outcome in patients with brain tumors. Here, we investigated IDH1-R132H expression in both gastric (n=526) and colorectal (n=399) tissues by performing immunohistochemistry analyses on tissue microarrays. We also tested whether IDH1-R132H expression correlated with various clinical parameters. In both gastric and colorectal cancer, expression of IDH1-R132H was associated with tumor stage. Patients with low IDH1-R132H expression had a poor overall survival. Our data indicate that IDH1-R132H expression could be used as a predictive marker of prognosis for patients with gastrointestinal cancer.