基于MDPs多肽组合的宫颈腺癌预警模型的构建、临床验证与机制研究

With the popularity of cervical and breast cancer screening, the incidence of cervical squamous cell carcinoma has obviously decreased, but incidence and mortality rate of cervical adenocarcinoma have not decreased. The early detection of cervical adenocarcinoma is difficult in low specificity, easily misdiagnosed. In the preliminary work, through the screening and two-stage verification, our research group screens out 6 peptides (MDPs) which originated from the same family (Mucin), with differential expression in cervical adenocarcinoma and healthy women, which has not been reported yet. After double-blind validation, we established an early warning model of cervical adenocarcinoma based on the MDPs peptides. Preliminary experimental results and literature reports support the possibility and feasibility of the MDPs peptides combination as the marker for cervical adenocarcinoma. Based on this, the project aims to explore relation between MDPs peptides differential expression and pathological grading and clinical stages of cervical adenocarcinoma, clarify their role and mechanism in the occurrence and progression of cervical adenocarcinoma, and using MDPs peptides establish a cervical adenocarcinoma early warning platform. It is convenient to make sample of cervical mucus without any trauma. From the peptides to explore the pathogenesis and prediction means of cervical adenocarcinoma, has the source of innovation. If the research is successful, no doubt can provide help for the prevention and treatment of cervical cancer.

两癌筛查的普及，使宫颈鳞癌发病率明显下降，而未改善腺癌的发病率及死亡率。目前，宫颈腺癌的早期发现存在特异性低、易漏诊误诊等困难。课题组在前期工作中，经过筛选与两阶段验证，发现了6条在宫颈腺癌和健康女性宫颈粘液中表现差异性的、来源于同一家族（Mucin）的多肽（MDPs），其研究未见报道；经双盲验证，我们初步建立了基于上述MDPs多肽组合的宫颈腺癌预警模型。预实验结果和文献报道支持该多肽组合具备作为宫颈腺癌标志物的可能性和可行性。本项目拟探寻MDPs多肽的差异性表现与宫颈腺癌癌变及病理分级/临床分期之间的关系，并阐明它们在宫颈腺癌发生/病程进展中的作用与机制，从而建立一个基于MDPs多肽组合的宫颈腺癌预警模型。宫颈粘液取材简便，无创伤性，从其中的多肽角度来探寻宫颈腺癌的发病预测手段，具有源头创新性。若研究成功，将为宫颈癌的防治提供帮助。

宫颈癌是女性最常见的恶性肿瘤之一，虽然两癌筛查已经普及，但宫颈腺癌的发病率并未改善，反而呈现上升及年轻化趋势。因此，寻找宫颈腺癌的有效标志物及其早期诊断手段刻不容缓。由于宫颈粘液中含丰富的蛋白/多肽，本研究旨在从中寻找潜在的多肽肿瘤标志物并建立宫颈腺癌的预警模型。.本研究选取宫颈腺癌患者/健康者的宫颈粘液样本或组织样本，利用液相色谱/串联质谱连用(LC-MS/MS）进行检测，获得内源性多肽或蛋白，筛选差异在三倍以上(t-test, FDR＜0.05）的多肽活蛋白。经统计学分析，从中进一步筛选出差异性多肽或蛋白。应用GO、KEGG等对差异多肽的蛋白前体以及差异蛋白进行功能分析，挖掘潜在的生物学功能。并通过细胞实验和构建动物模型进行验证和机制研究，从而建立具有良好的临床实用性的宫颈腺癌预警模型。.本课题研究为宫颈腺癌的早期诊断、预后判断、动态监测提供依据，为宫颈腺癌的防治提供新思路与新线索，具有显著的研究价值与良好的社会意义。