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Microengineered Technologies for Quantitative, Multiplexed and Spatially Resolved Measurement of miRNA in Tissue Sections

用于组织切片中 miRNA 的定量、多重和空间分辨测量的微工程技术

基本信息

批准号：
10407515
负责人：
Patrick S Doyle
金额：
$ 34.76万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-10 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10407515
关键词：
3-Dimensional Address Area Biological Biological Assay Biological Markers Biopsy Cancer Patient Cancer Prognosis Cells Clinical Complement Cytotoxic agent Data Data Analyses Diagnosis Diagnostic Disease Drug resistance Engineering Exhibits Formalin Gel Gene Expression Genetically Engineered Mouse Goals Heterogeneity Home Human Hydrogels Image Immunotherapy Individual Lung Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Measurement Measures Messenger RNA MicroRNAs Mus Mutation Organ Organoids Paraffin Embedding Pathologic Pathologist Pathology Pathway interactions Patients Pattern Performance Pharmaceutical Preparations Pharmacotherapy Phenotype Process RNA Relapse Reproducibility Research Research Personnel Resistance Resolution Sampling Slice Slide Specimen Stains System Techniques Technology Testing Therapeutic Time Tissue Embedding Tissue Sample Tissues Tumor Tissue Xenograft procedure anticancer research base cancer biomarkers cancer diagnosis clinically relevant data acquisition design experience innovation large datasets large scale production lithography miRNA expression profiling microRNA biomarkers microsystems multiplex detection neoplastic cell novel patient prognosis personalized medicine preservation prognostic provider adoption scale up software development standard of care targeted treatment therapy resistant tissue mapping tool treatment strategy tumor tumor heterogeneity

项目摘要

Project Summary Tumor heterogeneity is emerging as a major focus of cancer research. Tumors of many organs, including of the lung, exhibit intra-tumoral heterogeneity and different regions of a tumor can have varying resistance to therapies. A better understanding of tumor heterogeneity prior to treatment could be used for more personalized, informed treatments resulting in a better prognosis for patients. Formalin-fixed, paraffin-embedded (FFPE) sectioning of cancer specimens followed by cell staining is standard practice in pathological diagnosis. Unlike longer RNAs, microRNAs (miRNAs) can withstand the FFPE process and are known to be dysregulated in many diseases, especially cancer. Despite promise of miRNAs as sensitive and robust markers for cancer diagnosis and prognosis, there is no technology that can perform a quantitative, multiplexed detection of miRNA biomarkers from tumor tissue sections while preserving the spatial information of tumor biopsies and not being labor-intensive. The goal of this project is to develop tools to spatially and quantitatively resolve multiple miRNA biomarkers within pathological tissue sections. The proposed goals will be achieved via the following specific aims: 1) establishing a gel-post microwell platform for local miRNA measurement in small regions of tissue sections, 2) scaling up the sensing array and advancing the sample handling and data analysis, and 3) demonstrating the utility of the integrated system on patient-derived organoid and mouse xenograft samples, and genetically engineered mouse models. We have assembled a team of engineers and pathologists to achieve these goals. The technologies will be developed in a manner such that they integrate into and complement the current workflow of pathologists, thus providing a pathway to widespread adoption by clinicians. The project is innovative because no technology currently exists to perform spatially resolved miRNA expression profiles in clinically relevant FFPE tissue samples. The project is significant because it will provide researchers and pathologists a better understanding of tumor heterogeneity prior to treatment which could be used for more personalized, informed treatments resulting in a better prognosis for patients. The long-term goal is to include this assay in the standard of care tissue-based biomarker workup of every cancer patient.

项目总结