BackgroundPrevious evidence have demonstrated that p21-activated kinase PAK4 was correlated with breast cancer. The aim of this paper is to study the expression and interaction of p21-activated kinase (pAK)-4 and P54 protein in breast cancer.MethodsA total of 80 patients were enrolled in our study (breast fibroma n = 20, breast noninvasive cancer n = 20, early breast invasive cancer n = 20, and advanced breast invasive cancer). The expression of PAK4 was detected by immunohistochemical S-P method, and the relationship between them and the different pathological characteristics were compared. The subcellular localization of P54 and PAK4 in vitro was observed by immunofluorescence assay.ResultsThe expression of both PAK4 and P54 in breast cancer was much higher than that in breast fibroma. Meanwhile, we found that both PAK4 and P54 increased gradually as breast cancer progressed (advanced invasive > early invasive > noninvasive). The positive staining of P54 were mainly located in the cytoplasm, especially around the nucleus. There was no significant stained region in the cell matrix. The P54 localization in the cytoplasm was verified by confocal experiment, and the PAK4 was co-localized.ConclusionsPAK4 and P54 proteins may be used as molecular markers for diagnosis and treatment of breast cancer.

Time synchronization is a key technique in large-scale wireless sensor network applications. In order to tackle the problems of multi-hop synchronization error accumulation, clock frequency skew swinging, and network topology changes, a time synchronization protocol based on dynamic routing and forwarding certification (DRFC-TSP) is proposed in this paper. During the time synchronization process, a reference node with fewer synchronization hops and a more stable clock frequency is selected for every single hop, in order to obtain the best synchronization route. In this way, synchronization error accumulation can be restrained and the impact of clock frequency skew swinging on the time synchronization precision can be reduced. Furthermore, changes of the network topology can be well adapted by dynamic routing, in which the reference node is updated in every synchronization round. In the forwarding certification process, the status of nodes forwarding synchronous information outwards is authored by information exchange between neighboring nodes. Only synchronous information of the certificated nodes with a better performance can be forwarded. The network traffic can be decreased and the time synchronization precision can also be ensured, even with less energy consumption. Feasibility testing in large-scale wireless sensor networks is verified on NS2 simulation and more performances are evaluated on an embedded Linux platform.

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The authors assessed treatment and control of blood glucose, blood pressure (BP), and blood lipids among patients from Inner Mongolia with diabetes mellitus (DM) and hypertension (HTN) and identified the modifiable factors associated with treatment and achievement of blood glucose, BP, and blood lipid targets. The authors used a multistage stratified cluster sampling method according to geographical location and level of economic development in Inner Mongolia. Among patients with DM and HTN, the crude rates of fasting plasma glucose (FPG) treatment and control was 30.76% and 4.73%, respectively. Crude rates of BP treatment and control were 50.81% and 8.70%, respectively. The authors found that treatment rates of HTN and DM and control rates of BP and FPG showed a gradually increasing trend with increased age. Among patients with DM and HTN, the likelihood of treatment for HTN and DM was significantly increased among participants who were older, non-Mongolian, male, obese, smokers, and those with previous cardiovascular disease. The authors found that control of BP, FPG, and low-density lipoprotein cholesterol was far from optimal among study participants. Medical and health departments in Inner Mongolia should take appropriate measures to reduce the burden of DM and HTN in the population, such as by promoting and improving the quality of HTN and DM treatment to achieve control goals and reduce the risk of cardiovascular disease.

Background Effective biomarkers play a critical role in improving clinical approaches to treat lung adenocarcinoma (LUAD). However, many existing biomarkers have limitations due to a lot of factors, requiring the development of additional biomarkers to effectively predict the disease course and prognosis of LUAD. Guanine-rich RNA sequence binding factor 1 (GRSF1) participates in multiple biological processes, but its regulatory effect on LUAD remains unknown. The present study aimed to investigate the clinicopathological importance and biological role of GRSF1 in LUAD. Methods The expression of GRSF1 was evaluated using multiple service portals. X-Tile software were used to determine the high and low GRSF1 groups and the relationships between GRSF1 expression and clinicopathological characteristics were then analyzed by R packages. Besides, prognostic significance was identified by the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (K-M) Plotter. Overall survival (OS) and disease-free survival (DFS) was the main outcome of prognosis analysis. The DNA copy number alterations (CNAs) and methylations were calculated using cBioPortal and R packages. The co-expressed genes of GRSF1 were obtained from LinkedOmics, and functional networks were then constructed by R clusterProfiler. Additionally, cell counting kit 8 (CCK-8) and colony formation assays were applied to verify the proliferation effects of GRSF1 on LUAD cells. Results GRSF1 was significantly upregulated in the LUAD tissues compared to the non-tumor lung tissues (all P<0.05), and its expression was significantly correlated with gender (χ 2 =6.873, P=0.009) and T classification (χ 2 =13.62, P=0.003). Higher GRSF1 expression indicated worse OS [hazards ratio (HR) =1.6, P=0.0022] and DFS (HR =1.4, P=0.043), which suggested that GRSF1 was an independent prognostic factor for LUAD. DNA gain/amplification and hypomethylation may also contribute to GRSF1 upregulation. The functional annotation showed that GRSF1 regulates tumorigenesis through several signaling pathways. The knockdown of GRSF1 significantly suppressed lung cancer cell proliferation in vitro . Conclusions The high expression of GRSF1 indicated an unfavorable prognosis and was closely related to LUAD tumor occurrence and development, which could be used as an effective prognostic biomarker for patients suffering from LUAD.

#3041 PR expression is inversely associated with the stage of breast cancer and loss of PR is associated with more aggressive phenotype suggesting that PR has a protective role in established cancer. However, animal models and clinical studies showed that progesterone (PG) and PR is a risk factor for breast cancer development. The mechanism of these distinct actions of PG/PR in breast cancer is not known. PR contains a polyproline domain (PPD), which binds to the SH3 domain of c-Src. PR-SH3 interaction mediates activation of Src and MAPK and PG-mediated cell cycle progression. PR-BΔSH3, which has mutations in PPD, failed to mediate these effects. To access the biological role of PR extra-nuclear signaling mediated by PPD, PR-B, PR-BΔSH3 or vector control were stably expressed in non-transformed mammary epithelial MCF10A cell and in breast cancer cells, MCF-7 and T47DY. Cells were tested for their transformation potential by growth in soft-agar and in 3-D cultures. In MCF10A model, cells expressing PR-BΔSH3 showed an increase in both colony numbers and sizes while cells expressing PR-B showed little growth in soft-agar in the absence of PG and PG strongly inhibited colony formation. In MCF-7 cells, both cells expressing PR-B and PR-BΔSH3 formed colonies in the absence of PG and PG strongly inhibited colony formation in cells expressing PR-B but had no effects in cells expressing PR-BΔSH3. To mimic growth in vivo, cells were grown in 3D cultures. MCF-10A expressing vector control or PR-B formed polarized acini with hollow lumen while cells expressing PR-BΔSH3 formed large and filled acini. Using Ki-67 and E-cadherin immunostaining, cells expressing PR-BΔSH3 showed an increase in cells proliferation and a break down in E-caderin as compared to cells expressing PR-B or vector control. Similar changes in cells expressing PR-BΔSH3 were also found in MCF-7 model. We next determined the influence of PR PPD on cell morphology and motility in T47DY PR- cells. T47DY expressing PR-B were rounded and epithelial-like as compared to cells expressing PR-BΔSH3 or LacZ, which were large, flat and mesenchymal-like. Cells expressing PR-B showed a decrease in cell motility with few focal adhesions and were devoid of actin stress fibers, as compared to cells expressing PR-BΔSH3 and LacZ. Similar changes were also observed in MCF-7 cell series. Thus, PR PPD appears to play a role in epithelial-mesenchymal transition (EMT) of breast cancer cells. Interestingly, effects of PR-B on these cellular functions are independent of ligand, but dependent upon PR PPD. Using DNA microarrays, gene expression of T47DY expressing PR-B and PR-BΔSH3 were compared. Gene ontogeny analysis of genes regulated by PPD in unliganded receptor revealed an enrichment of genes involved in regulation of key cellular processes including cell polarity, motility, EMT, NF-KB, TGF-β, and Wnt signaling. Results from DNA microarrays demonstrate that extra-nuclear signaling of PR through PPD interactions has a profound effect on PR regulated gene in the absence of PG and may plays an important role in mediating differentiating effects of PR. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3041.

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Background: Mutation in titin (TTN), associated with a worsened prognosis, is among the most common genetic variants in human hepatocellular carcinoma. mRNA expression data and TTN mutation information from TCGA cohort were utilized to characterize a specific TTN-mutation-associated signature according to gene-expression differences between wild type (TTN-WT) and TTN-mutated (TTN-MUT) hepatocellular carcinoma (HCC) patients. In total, 189 differentially expressed genes (DEGs) potentially correlated with TTN mutation status were identified. Five genes (VAX1, MMP3, CXCL5, TKTL1 and KCNA3), identified by univariate Cox regression and Kaplan-Meier survival analyses, constituted an independent OS prognostic gene signature in HCC patients. Depending on this gene signature, patients were grouped into high- and low-risk subgroups and a significant enrichment associated with immunity is detected between the risk groups. In addition, the high-risk group was associated with an abundance of macrophages and neutrophils, while the infiltration indices of T follicular helper cells, natural killer cells, and type 2 helper T cells (Th2) were lower compared to low-risk group. In the multivariate Cox regression model, the five-gene signature remained a significant predictor independent of other conventional clinical risk factors used for survival prediction in HCC patients. MMP3 and CXCL5 expression were further validated in HCC cell lines.Results: We established a novel and unique TTN-mutation-related gene signature for survival outcome prediction for HCC patients. Conclusion: Our research foundings display a specific mechanism of TTN mutation and hold promise for the identification of HCC patients with poor prognosis.