需求变更影响分析模型及相关技术研究

需求是后续开发活动的基准，早期的一些研究者认为应该在需求完全确定之后再进行后续开发，Royce所提出的瀑布模型就是这种思想的一个体现。但是，实践经验告诉我们，不管前期的需求分析做的多么完美，需求还是会发生变更。一方面是因为需求本身很复杂，对它的分析、理解和描述是一个循序渐进的过程，不可能一蹴而就；另一方面由于用户期望和偏好的改变、市场环境的转变、使用环境的日益复杂、技术的革新等都会使得原有的软件系统无法满足各涉众的利益。因此，需求变更是软件开发中固有的规律，是不可避免和普遍存在的。 需求变更通常会导致需求间及需求与后续工作产品间的不一致。因此，频繁的需求变更会造成产品质量下降、进度延期、成本超支等问题。变更影响分析(Change Impact Analysis)通过分析变更对象及其相关工作产品间的关系来评估变更造成的影响，从而控制变更。现有方法多数是从软件维护的角度，对代码的变更影响进行分析，过于细节和技术化，不能对需求变更影响分析提供有力支持。即使针对需求变更的影响分析方法也只是基于形式化需求规约，通过分析需求间的关系来识别影响范围，并未考虑需求变更对后续工作产品造成的影响，同时形式化需求规约的应用困难也限制了该方法的实用性。此外，随着需求和工作产品的规模与复杂性日益增加，使得手工建立和维护需求间及需求与工作产品间关系面临着不小的难度。 基于以上分析，本文提出了针对自然语言需求规约的需求变更影响分析模型RCIAM (Requirement Change Impact Analysis Model)，围绕着如何自动识别和筛选需求间的关系——横向需求跟踪关系(Horizontal Requirement Traceability)、如何自动识别和筛选需求与工作产品间的关系——纵向需求跟踪关系(Vertical Requirement Traceability)、如何较全面的进行需求变更影响计算和决策三个问题展开了研究。 本文的主要贡献有： (1) 提出了需求变更影响分析模型RCIAM 本文对RCIAM进行了形式化定义。该模型不但提供了需求变更影响分析算法和对决策的支持，还提供了自动识别横向和纵向需求跟踪关系的方法。RCIAM主要包含数据处理和数据分析两个层次。数据处理层采用了文本处理(Text Processing)技术实现了横向和纵向需求跟踪关系的自动识别，为数据分析层提供需求跟踪关系数据；数据分析层基于需求跟踪关系数据，在产生需求变更申请(Change Request)时，进行量化影响计算，并提供决策支持。 (2) 提出了横向需求跟踪关系的识别与筛选方法 在对自然语言需求规约文档进行深入分析后，我们发现了两种与需求变更影响密切相关的关系类型，并从文本相似性的角度将它们定义为相似跟踪关系和引用跟踪关系。在将需求项拆分为需求片段的基础上，利用信息检索技术(Information Retrieval，IR)计算需求片段间的文本相似度，并设计了相应的算法对相似跟踪关系和引用跟踪关系进行自动识别。最后，提出了“变更影响跟踪”的规则来辅助对候选跟踪关系的人工筛选。 (3) 提出了纵向需求跟踪关系的识别与筛选方法 已有的研究多采用IR技术来自动建立需求与工作产品之间的跟踪关系，但是却存在着精度不理想的问题。我们从查全率(Recall)和查准率(Precision)的角度，分析了应用IR技术自动建立需求与代码跟踪关系的方法中产生的错误关系，发现了造成精度问题的根源所在。依据这一发现，基于现有方法，本文方法加入了相关反馈(Relvant Feedback)辅助识别和代码注释信息辅助识别等改进措施，并提供了人工筛选策略。 (4) 提出了需求变更影响分析计算与决策方法 本文通过矩阵运算说明了需求变更影响通过需求跟踪关系传播到其它需求和工作产品的过程，并设计了相应的需求变更影响分析算法。该算法考虑变更发生在不同阶段时对不同类型工作产品的影响，采用变更类型和关系强度两个因子加权计算影响值，并提出了根据影响值来进行变更决策的方法。 (5) 应用研究 结合中科方德公司Qone平台的开发，对以上工作进行了应用研究和性能分析。在Qone平台的需求管理工具版本1.0的开发中，首先采用本文方法对横向和纵向需求跟踪关系进行了自动识别，然后对开发期间发生的十次需求变更申请进行了影响分析和决策。在项目完成后，设计了实验对横向和纵向需求跟踪关系的识别进行了性能分析。结果表明，本文方法能够有效辅助进行需求变更影响分析。

AUV定位信号检测延时的蒙特卡洛模拟分析

在简要介绍AUV声学定位声纳接收机原理基础上,分析了CW脉冲信号在极性相关检测电路中的传输过程,建立了极性相关积分检测延时仿真分析模型。提出采用蒙特卡洛模拟方法获取检测延时的分布特征和统计参数的观点。实验结果表明蒙特卡洛模拟实验与硬件电路实验结果一致,对于解决随机性检测延时问题具有很强的能力。获得的结果可为AUV定位声纳检测门限的设定、声学测距和定位精度分析以及水声通信延时分析提供参考。

财政预测模型研究及应用

采用多种科学预测方法与财政经济实际相结合的方式建立了一个综合的财政收支系统动力学模型．这个模型集中了时间序列分析模型，灰色系统预测模型的参数综合性强和系统动力学模型结构分明，用动态反馈方式预测系统发展变化的特点，对东北两大城市预算内财政收支“八五”计划指标进行了全面定量的预测与分析，得到了很好的应用效果。

复杂应力环境下断续节理岩体真三轴实验研究及其工程应用

The great deal of joints and faults , existing in the rock mass , are the leading cause of discontinuous rock mass. Structural planes not only destroy the integrality of rock mass, but also lead nonlinearity、heterogeneity、anisotropy and failure mode on mechanical properties of rock mass. Therefore the selection of strength and deformation parameters was very difficult. In practical rock mass engineering, equivalent parameters of rock mass were selected by the method of expert experience and engineering analogy. Based on the fine description of discontinuous joints in the type Ⅳ and Ⅴ rock mass and geological survey datum in situ, models was obtained by generalizing the structure of rock mass by the method of statistical analysis. Model intensity and deformation test were carried out on the true triaxial apparatus. Intermediate principle stress effect, anisotropy and dimension effect of discontinuous rock mass were considered in the model test. 3-D correction to Hoek-Brown empirical criterion was done by analysed the test datum. Detailed works were listed as follows: (1) The factors influenced intensity and deformation of discontinuous joints rock mass were the value of 、continuity, density and included angle of joints and anisotropy of joint plane. True triaxial intensity and deformation tests were carried out by considering above factors. The influence rule was obtained and corresponding relation formulary was established； (2) Based on the true triaxial tests under different stress path and load modes, we obtain intensity and deformation rule of rock mass； (3) Based on a great deal of true triaxial tests and other test datum, correction to the Hoek-Brown empirical criterion was done in the chapter 4. The intermediate principle stress was considered in the corrected formulary. It indicated that the formulary was applicable under a certain condition. In addition, the yield plane form of corrected Hoek-Brown empirical criterion under principle stress space was described in the paper. And the question of corner of yield plane was discussed； (4) Based on the single discontinuity theory, the three-dimensional intensity formulary of discontinuous joint rock mass was established. Correction to the intensity formulary was done considering intermediate principle stress effect. We may obtain the conclusion that the intensity of the discontinuous joint rock mass was influenced on compositive factors. They were 、 、continuity、internal frictional angle and cohesiveness of joint plane and rock； (5) The results of the true triaxial model test was applied into parameters evaluation of dam foundation rock mass of JinPing hydropower station. For there were abundant ophicalcite in the dam foundation, the interval of intensity and formation parameters influenced on continuity were determined based on test datum. (6) Especial mould for prismatic jointing model was designed. True triaxial intensity and deformation tests by Basalt with prismatic jointing were carried out. The influence of intermediate principle stress, stress path, anisotropy effect and dimensional effect to intensity and deformation was discussed in the chapter 6. The work of (3)、(4)、(6) was significative supplement and innovation to current test and theory.

基于精细结构描述及数值试验的断续节理岩体力学参数智能选取

Evaluating the mechanical properties of rock masses is the base of rock engineering design and construction. It has great influence on the safety and cost of rock project. The recognition is inevitable consequence of new engineering activities in rock, including high-rise building, super bridge, complex underground installations, hydraulic project and etc. During the constructions, lots of engineering accidents happened, which bring great damage to people. According to the investigation, many failures are due to choosing improper mechanical properties. ‘Can’t give the proper properties’ becomes one of big problems for theoretic analysis and numerical simulation. Selecting the properties reasonably and effectively is very significant for the planning, design and construction of rock engineering works. A multiple method based on site investigation, theoretic analysis, model test, numerical test and back analysis by artificial neural network is conducted to determine and optimize the mechanical properties for engineering design. The following outcomes are obtained: (1) Mapping of the rock mass structure Detailed geological investigation is the soul of the fine structure description. Based on statistical window，geological sketch and digital photography，a new method for rock mass fine structure in-situ mapping is developed. It has already been taken into practice and received good comments in Baihetan Hydropower Station. (2) Theoretic analysis of rock mass containing intermittent joints The shear strength mechanisms of joint and rock bridge are analyzed respectively. And the multiple modes of failure on different stress condition are summarized and supplied. Then, through introducing deformation compatibility equation in normal direction, the direct shear strength formulation and compression shear strength formulation for coplanar intermittent joints, as well as compression shear strength formulation for ladderlike intermittent joints are deducted respectively. In order to apply the deducted formulation conveniently in the real projects, a relationship between these formulations and Mohr-Coulomb hypothesis is built up. (3) Model test of rock mass containing intermittent joints Model tests are adopted to study the mechanical mechanism of joints to rock masses. The failure modes of rock mass containing intermittent joints are summarized from the model test. Six typical failure modes are found in the test, and brittle failures are the main failure mode. The evolvement processes of shear stress, shear displacement, normal stress and normal displacement are monitored by using rigid servo test machine. And the deformation and failure character during the loading process is analyzed. According to the model test, the failure modes quite depend on the joint distribution, connectivity and stress states. According to the contrastive analysis of complete stress strain curve, different failure developing stages are found in the intact rock, across jointed rock mass and intermittent jointed rock mass. There are four typical stages in the stress strain curve of intact rock, namely shear contraction stage, linear elastic stage, failure stage and residual strength stage. There are three typical stages in the across jointed rock mass, namely linear elastic stage, transition zone and sliding failure stage. Correspondingly, five typical stages are found in the intermittent jointed rock mass, namely linear elastic stage, sliding of joint, steady growth of post-crack, joint coalescence failure, and residual strength. According to strength analysis, the failure envelopes of intact rock and across jointed rock mass are the upper bound and lower bound separately. The strength of intermittent jointed rock mass can be evaluated by reducing the bandwidth of the failure envelope with geo-mechanics analysis. (4) Numerical test of rock mass Two sets of methods, i.e. the distinct element method (DEC) based on in-situ geology mapping and the realistic failure process analysis (RFPA) based on high-definition digital imaging, are developed and introduced. The operation process and analysis results are demonstrated detailedly from the research on parameters of rock mass based on numerical test in the Jinping First Stage Hydropower Station and Baihetan Hydropower Station. By comparison，the advantages and disadvantages are discussed. Then the applicable fields are figured out respectively. (5) Intelligent evaluation based on artificial neural network (ANN) The characters of both ANN and parameter evaluation of rock mass are discussed and summarized. According to the investigations, ANN has a bright application future in the field of parameter evaluation of rock mass. Intelligent evaluation of mechanical parameters in the Jinping First Stage Hydropower Station is taken as an example to demonstrate the analysis process. The problems in five aspects, i. e. sample selection, network design, initial value selection, learning rate and expected error, are discussed detailedly.

人口统计信息空间可视化系统研究

Population research is a front area concerned by domestic and overseas, especially its researches on its spatial visualization and its geo-visualization system design, which provides a sound base for understanding and analysis of the regional difference in population distribution and its spatial rules. With the development of GIS, the theory of geo-visualization more and more plays an important role in many research fields, especially in population information visualization, and has been made the big achievements recently. Nevertheless, the current research is less attention paid to the system design for statistical-geo visualization for population information. This paper tries to explore the design theories and methodologies for statistical-geo-visualization system for population information. The researches are mainly focused on the framework, the methodologies and techniques for the system design and construction. The purpose of the research is developed a platform for population atlas by the integration of the former owned copy software of the research group in statistical mapping system. As a modern tool, the system will provide a spatial visual environment for user to analyze the characteristics of population distribution and differentiate the interrelations of the population components. Firstly, the paper discusses the essentiality of geo-visualization for population information and brings forward the key issue in statistical-geo visualization system design based on the analysis of inland and international trends. Secondly, the geo-visualization system for population design, including its structure, functionality, module, user interface design, is studied based on the concepts of theory and technology of geo-visualization. The system design is proposed and further divided into three parts: support layer, technical layer, user layer. The support layer is a basic operation module and main part of the system. The technical layer is a core part of the system, supported by database and function modules. The database module mainly include the integrated population database (comprises spatial data, attribute data and geographical features information), the cartographic symbol library, the color library, the statistical analysis model. The function module of the system consists of thematic map maker component, statistical graph maker component, database management component and statistical analysis component. The user layer is an integrated platform, which provides the functions to design and implement a visual interface for user to query, analysis and management the statistic data and the electronic map. Based on the above, China's E-atlas for population was designed and developed by the integration of the national fifth census data with 1:400 million scaled spatial data. The atlas illustrates the actual development level of the population nowadays in China by about 200 thematic maps relating with 10 map categories(environment, population distribution, sex and age, immigration, nation, family and marriage, birth, education, employment, house). As a scientific reference tool, China's E-atlas for population has already received the high evaluation after published in early 2005. Finally, the paper makes the deep analysis of the sex ratio in China, to show how to use the functions of the system to analyze the specific population problem and how to make the data mining. The analysis results showed that: 1. The sex ratio has been increased in many regions after fourth census in 1990 except the cities in the east region, and the high sex ratio is highly located in hilly and low mountain areas where with the high illiteracy rate and the high poor rate; 2. The statistical-geo visualization system is a powerful tool to handle population information, which can be used to reflect the regional differences and the regional variations of population in China and indicate the interrelations of the population with other environment factors. Although the author tries to bring up a integrate design frame of the statistical-geo visualization system, there are still many problems needed to be resolved with the development of geo-visualization studies.

工程地质三维可视化技术及其工程应用研究

Study of 3D visualization technology of engineering geology and its application to engineering is a cross subject which includes geosciences, computer, software and information technology. Being an important part of the secondary theme of National Basic Research Program of China (973 Program) whose name is Study of Multi-Scale Structure and Occurrence Environment of Complicated Geological Engineering Mass(No.2002CB412701), the dissertation involves the studies of key problems of 3D geological modeling, integrated applications of multi-format geological data, effective modeling methods of complex approximately layered geological mass as well as applications of 3D virtual reality information management technology.The main research findings are listed below:Integrated application method of multi-format geological data is proposed,which has solved the integrated application of drill holes, engineering geology plandrawings, sectional drawings and cutting drawings as well as exploratory trenchsketch. Its application can provide as more as possible fundamental data for 3Dgeological modeling.A 3D surface construction method combined Laplace interpolation points withoriginal points is proposed, so the deformation of 3D model and the crossing error ofupper and lower surface of model resulted from lack of data when constructing alaminated stratum can be eliminated.3D modeling method of approximately layered geological mass is proposed,which has solved the problems of general modeling method based on the sections or points and faces when constructing terrain and concordant strata.The 3D geological model of VII dam site of Xiangjiaba hydropower stationhas been constructed. The applications of 3D geological model to the auto-plotting ofsectional drawing and the converting of numerical analysis model are also discussed.3D virtual reality information integrated platform is developed, whose mostimportant character is that it is a software platform having the functions of 3D virtualreality flying and multi-format data management simultaneously. Therefore, theplatform can load different 3D model so as to satisfy the different engineeringdemands.The relics of Aigong Cave of Longyou Stone Caves are recovered. Thereinforcement plans of 1# and 2# cave in phoenix hill also be expressed. The intuitiveexpression provided decision makers and designers a very good environment.The basic framework and specific functions of 3D geological informationsystem are proposed.The main research findings in the dissertation have been successfully applied to some important engineering such as Xiangjiaba hydropower station, a military airport and Longyou Stone Caves etc.

Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

The standard early markers for identifying and grading HIE severity, are not sufficient to ensure all children who would benefit from treatment are identified in a timely fashion. The aim of this thesis was to explore potential early biomarkers of HIE. Methods: To achieve this a cohort of infants with perinatal depression was prospectively recruited. All infants had cord blood samples drawn and biobanked, and were assessed with standardised neurological examination, and early continuous multi-channel EEG. Cord samples from a control cohort of healthy infants were used for comparison. Biomarkers studied included; multiple inflammatory proteins using multiplex assay; the metabolomics profile using LC/MS; and the miRNA profile using microarray. Results: Eighty five infants with perinatal depression were recruited. Analysis of inflammatory proteins consisted of exploratory analysis of 37 analytes conducted in a sub-population, followed by validation of all significantly altered analytes in the remaining population. IL-6 and IL-6 differed significantly in infants with a moderate/severely abnormal vs. a normal-mildly abnormal EEG in both cohorts (Exploratory: p=0.016, p=0.005: Validation: p=0.024, p=0.039; respectively). Metabolomic analysis demonstrated a perturbation in 29 metabolites. A Cross- validated Partial Least Square Discriminant Analysis model was developed, which accurately predicted HIE with an AUC of 0.92 (95% CI: 0.84-0.97). Analysis of the miRNA profile found 70 miRNA significantly altered between moderate/severely encephalopathic infants and controls. miRNA target prediction databases identified potential targets for the altered miRNA in pathways involved in cellular metabolism, cell cycle and apoptosis, cell signaling, and the inflammatory cascade. Conclusion: This thesis has demonstrated that the recruitment of a large cohortof asphyxiated infants, with cord blood carefully biobanked, and detailed early neurophysiological and clinical assessment recorded, is feasible. Additionally the results described, provide potential alternate and novel blood based biomarkers for the identification and assessment of HIE.

Xanthoria parietina as a biomonitor of airborne heavy metal pollution in forest sites in the North East of Morocco

Xanthoria parietina, common foliose lichen, growing in its natural habitat, was analysed for the concentration of five heavy metals (Fe, Cr, Zn, Pb and Cu) from different forest sites of North East of Morocco (Kenitra, Sidi Boughaba, Mkhinza, Ceinture Verte near Temara city, Skhirate, Bouznika and Mohammedia). The quantification was carried out by inductively coupled plasma - atomic emission spectrometry (ICP-AES). Results were highly significant p<0,001. The concentration of metals is correlated with the vehicular activity and urbanization. The total metal concentration is highest at the Kenitra area, followed by Ceinture Verte site near Temara city, which experience heavy traffic throughout the year. Scanning electron microscopy (SEM) of particulate matter on lichen of Xanthoria parietina was assessed as a complementary technique to wet chemical analysis for source apportionment of airborne contaminant. Analysis revealed high level of Cu, Cr, Zn and Pb in samples near roads.  

The conflict between realism and abstraction in the field of spanish art as an iteration of la "Querelle des Anciens et des Modernes"

Based on the analysis model favored by the study of the conditions in which the seventeenth century Querelle des Anciens et des Modernes took place, we examine the case of confrontation between realism and abstraction, which occurred in the context of Spanish art in the nineties of the twentieth century. Connections are established with other aesthetic conflicts which are considered part of a genealogy whose most explicit antecedent could be placed in the before mentioned complaint, such as the confrontation between realism and abstraction in the American art scene, which occurred in the fifties of the last century, and the more recent controversy on pluralism and the end of art.

Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile-Associated Diarrhea in Hospitalized Patients

The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.02/100 bed-days), fluoroquinolone use (average delay = 3 months; variation of CDAD incidence = 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay = 1 month; variation of CDAD incidence = 0.002/100 bed-days), and macrolide use (average delay = 5 months; variation of CDAD incidence = 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay = 1 month; variation of CDAD incidence = 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect.

Automated mixed dimensional modelling from 2D and 3D CAD models

The motivation for this paper is to present procedures for automatically creating idealised finite element models from the 3D CAD solid geometry of a component. The procedures produce an accurate and efficient analysis model with little effort on the part of the user. The technique is applicable to thin walled components with local complex features and automatically creates analysis models where 3D elements representing the complex regions in the component are embedded in an efficient shell mesh representing the mid-faces of the thin sheet regions. As the resulting models contain elements of more than one dimension, they are referred to as mixed dimensional models. Although these models are computationally more expensive than some of the idealisation techniques currently employed in industry, they do allow the structural behaviour of the model to be analysed more accurately, which is essential if appropriate design decisions are to be made. Also, using these procedures, analysis models can be created automatically whereas the current idealisation techniques are mostly manual, have long preparation times, and are based on engineering judgement. In the paper the idealisation approach is first applied to 2D models that are used to approximate axisymmetric components for analysis. For these models 2D elements representing the complex regions are embedded in a 1D mesh representing the midline of the cross section of the thin sheet regions. Also discussed is the coupling, which is necessary to link the elements of different dimensionality together. Analysis results from a 3D mixed dimensional model created using the techniques in this paper are compared to those from a stiffened shell model and a 3D solid model to demonstrate the improved accuracy of the new approach. At the end of the paper a quantitative analysis of the reduction in computational cost due to shell meshing thin sheet regions demonstrates that the reduction in degrees of freedom is proportional to the square of the aspect ratio of the region, and for long slender solids, the reduction can be proportional to the aspect ratio of the region if appropriate meshing algorithms are used.

A framework for challenging deficits in compression bandaging techniques

Northern Irish (and all UK-based) health care is facing major challenges. This article uses a specific theory to recommend and construct a framework to address challenges faced by the author, such as deficits in compression bandaging techniques in healing venous leg ulcers and resistance found when using evidence-based research within this practice. The article investigates the challenges faced by a newly formed community nursing team. It explores how specialist knowledge and skills are employed in tissue viability and how they enhance the management of venous leg ulceration by the community nursing team. To address these challenges and following a process of reflection, Lewin's forcefield analysis model of change management can be used as a framework for some recommendations made.

Classification the geographical origin of corn distillers dried grains with solubles by near infrared reflectance spectroscopy combined with chemometrics: A feasibility study

In this study, 137 corn distillers dried grains with solubles (DDGS) samples from a range of different geographical origins (Jilin Province of China, Heilongjiang Province of China, USA and Europe) were collected and analysed. Different near infrared spectrometers combined with different chemometric packages were used in two independent laboratories to investigate the feasibility of classifying geographical origin of DDGS. Base on the same dataset, one laboratory developed a partial least square discriminant analysis model and another laboratory developed an orthogonal partial least square discriminant analysis model. Results showed that both models could perfectly classify DDGS samples from different geographical origins. These promising results encourage the development of larger scale efforts to produce datasets which can be used to differentiate the geographical origin of DDGS and such efforts are required to provide higher level food security measures on a global scale.

Sphingosine Kinase 1 Promotes Malignant Progression in Colon Cancer and Independently Predicts Survival of Patients With Colon Cancer by Competing Risk Approach in South Asian Population

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.

METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.

RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.

CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.