基于基因表达谱数据整合分析筛选出的DPYSL5基因在神经内分泌型前列腺癌发生发展中的作用及机制研究

Most of the small cell neuroendocrine carcinoma of prostate (NEPC) is transformed from classical prostate adenocarcinoma after endocrine therapy, it is a highly aggressive malignancy and has poor prognosis. NEPC is an important cause of the progression and death of about 25% of the advanced prostate cancer. At present, the tumor occurrence and evolution of molecular mechanism of this type of cancer is still not clear. DPYSL5 gene is one of the common differentially expressed genes obtained by gene expression profiling data integration analysis in the development of transformed neuroendocrine prostate cancer. Up to now, there is rare studies on DPYSL5 in carcinogesis and development of cancer. Moreover,it is still not clear about the molecular mechanisms and clinical significance of DPYSL5 as a novel key NEPC related gene. Our preliminary results show that DPYSL5 expression levels are higher in about 85% of NEPC samples, and the patients have shorter survival time with higher DPYSL5 expression level, which is the independent prognosis factor. In vitro study found that DPYSL5 expression are increased in NEPC cell lines as well. This proposed effort is on the basis of the hypothesis of " DPYSL5 plays a role on carcinogenesis and prognosis in NEPC as a new key gene". The large scale clinical samples and in vitro and in vivo experiments will be jointly used to illustrated the role of DPYSL5 in tumorgensis and progress in NEPC, the molecular mechanisms of DPYSL5 overexpression and inducing different molecular pathways will be explored as well. In order to explain the identity of the key regulated gene of DPYSL5, to provide advices for managment of the high-risk patients in clinic, and for the translational values as the potential biomarker or target for NEPC diagnosis and therapy.

神经内分泌型前列腺癌（NEPC）多由前列腺腺癌内分泌治疗后转化而来，预后极差，是约25%晚期前列腺癌进展和死亡的重要原因。目前其发生和演进的分子机制仍不清楚。本项目前期基于基因组转录数据整合分析筛选出一个NEPC差异表达基因DPYSL5。截至目前DPYSL5在肿瘤领域的研究不多，作为NEPC新的候选关键基因，其临床意义及分子机制都亟待阐明。我们前期通过检测79例NEPC标本，发现85%的样本癌组织中DPYSL5的表达明显升高，且多因素分析显示DPYSL5阳性表达是影响患者生存的独立不良因素，体外实验亦发现DPYSL5在NEPC细胞中表达上调。本项目基于“DPYSL5可能是NEPC发生发展中的关键基因”的假设，拟采用临床研究结合体内外实验方法，进一步验证DPYSL5在NEPC发生发展中的作用，阐释其基因表达上调的机理并探索DPYSL5介导的分子机制。从而为寻找NEPC潜在的诊治靶标提供依据。

多数晚期前列腺癌癌患者经过去势治疗后均转化为去势抵抗性前列腺癌（CRPC），此类患者预后极差，尤其是NEPC，无特殊有效的治疗办法。但是，目前其发生和演进的分子机制仍不清楚。本项目前期基于基因组转录数据整合分析筛选出一个NEPC差异表达基因CRMP5。截至目前CRMP5在肿瘤领域的研究不多，作为NEPC新的候选关键基因，其临床意义及分子机制都亟待阐明。本项目基于“CRMP5可能是NEPC发生发展中的关键基因”的假设，拟采用临床研究结合体内外实验方法，进一步验证CRMP5在NEPC发生发展中的作用，阐释其基因突变的机理并探索CRMP5介导的分子机制，从而为寻找NEPC潜在的诊治靶标提供依据。