项目来源

国家重点研发计划(NKRD)

项目主持人

陈刚

项目受资助机构

浙江大学医学院附属妇产科医院

项目编号

2022YFC2704302

立项年度

2022

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

321.00万元

学科

生育健康及妇女儿童健康保障

学科代码

未公开

基金类别

未公开

关键词

子宫内膜癌 ; 分子分型 ; Dalton-MIT试剂盒 ; POLE突变 ; 回顾性研究 ; 前瞻性队列研究 ; Endometrial cancer ; Molecular sub-typing ; Dalton-MIT kit ; POLE mutation ; Retrospective study ; Prospective cohort study

参与者

王新宇

参与机构

复旦大学附属妇产科医院；华中科技大学；浙江大学医学院附属第一医院

项目标书摘要：课题二本年度已完成的主要工作是优化内膜癌分子分型的检测方法，初步探讨从前分子分型在临床实践中费时费力、难以推广的问题。我们发现基于PCR技术的Dalton-MIT试剂盒能有效捕捉到多个POLE突变位点，具有良好的灵敏度与特异性，且与二代测序具有良好的一致性，该试剂盒能够有效推动内膜癌分子分型在临床中的推广应用，相关研究数据已经被Archives of Pathology and Laboratory Medicine期刊接收。同时，本课题组回顾性分析了2013年以来就诊于浙大妇院且完善病理分型的759名内膜癌患者的临床病理数据和跟踪随访资料，并运用优化版的分子分型方法进行样本检测，结合患者预后，证实优化的内膜癌的分子分型同样能够有效预测患者预后，这为分子分型的优化和临床推广提供了回顾性研究基础。此外，我们还发现基于免疫组化的MMR和p53突变检测对病理医生的要求较高，存在不能准确判读的可能性，这提示对内膜癌分子分型检测方法的优化还有许多工作值得开展推进。_x000D_本课题同时开展了基于前瞻性队列的分子分型数据验证阶段，从患者入组到随机分配再到患者术后的治疗和随访，目前整个临床研究的技术路线已经确立。13个临床中心共入组患者111例，处于有序的推进过程中，有望在计划时间内完成期望样本量的收集，按时开展后续构建异质性肿瘤3D模型，开发异质性细胞分型算法等研究工作及相应成果转化.

Application Abstract: The main work completed in this year is to optimize the detection method of molecular staging of endometrial cancer,and to explore the problems of time-consuming and difficult to promote the former molecular staging in clinical practice.We found that the Dalton-MIT kit based on PCR technology can effectively capture multiple POLE mutation sites with good sensitivity and specificity,and has good consistency with second-generation sequencing,which can effectively promote the molecular typing of endocardial cancer in the clinical application,and the related research data have been accepted by the Archives of Pathology and Laboratory Medicine.Meanwhile,our group retrospectively analyzed the clinicopathological data and follow-up data of 759 patients with endometrial cancer who had been diagnosed at Woman's Hospital of Zhejiang University since 2013,and applied the optimized molecular typing method to test the samples,and combined with the prognosis of the patients,it was confirmed that the optimized endometrial cancer molecular typing could also effectively predict the prognosis of the patients,which provided a retrospective basis for the optimization of the molecular typing and its promotion to the clinic.In addition,we also found that immunohistochemistry-based MMR and p53 mutation detection is more demanding for pathologists,and there is a possibility of inaccurate interpretation,which suggests that there is still a lot of work to be carried out to optimize the molecular typing detection methods for endometrial cancer.This project also carries out the validation phase of molecular typing data based on prospective cohort,from patient enrollment to random assignment to postoperative treatment and follow-up,the technical route of the whole clinical study has been established.111 patients have been enrolled in 13 clinical centers,which is in the process of orderly advancement,and it is expected to complete the collection of the desired sample size within the planned time,and then carry out the research work of constructing 3D models and developing algorithms of heterogeneous tumor typing in time.It is expected to complete the collection of the desired sample size within the planned timeframe,and carry out the subsequent research work of constructing 3D models of heterogeneous tumors and developing algorithms for heterogeneous cell typing,as well as translating the results into reality in a timely manner.

项目受资助省

浙江省