MRI and Metabolomics Biomarkers for Uterine Malignancy
Condition: Uterine Neoplasms
MeSH terms: Neoplasms; Uterine Neoplasms
Study type: Observational

Summary: 
      The aims of this project are: (1) To establish a research platform in order to integrate
      multiparametric imaging and metabolomics data for uterine malignancy. (2) Identify potential
      surrogate biomarkers for early diagnosis of endometrial cancer by using multiparametric
      magnetic resonance imaging and metabolomics approach. (3) To develop surrogate biomarkers for
      uterine malignancy, in detecting tumor involvement of myometrium, cervix, and lymph nodes.
      The investigators propose a 3-year research project to prospectively collect data from 150
      female patients 20-80 years old, with clinically diagnosed or suspected to have uterine
      malignancy. An additional control group comprising 30 patients with normal endometrial tissue
      will be enrolled. Robust magnetic resonance (MR) imaging techniques including MR spectroscopy
      (MRS), diffusion-weighted imaging and chemical exchange saturation transfer (CEST) imaging
      will be applied. Biological samples (tissue, blood, urine) will be analyzed by detailed
      metabolomics approach (high-resolution MRS).
    

Detailed description: 
      In the 1st year part of this project, the investigators aim to identify the differences
      between normal endometrium and cancer tissue. Standard conventional MR study plus MRS,
      diffusion-weighted imaging and CEST sequences will be carried out on 30 eligible surgical
      candidates for pretreatment clinical assessment.Metabolites in cancer tissue will be
      collected during operation and analyzed using high resolution MRS, and compared with control
      group. The primary endpoint of this part is to identify different imaging and metabolomic
      profiles between normal and cancer subjects. In the 2nd year, the investigators will continue
      accumulate case number, in order to evaluate the diagnostic accuracy of advanced MR imaging
      and metabolomics biomarker, in prediction of T staging and myometrial involvement. By the end
      of 3rd year, the investigators will collect 150 patients, with approximately 20 cases with
      cervical invasion and 20 cases with nodal metastasis, in order to answer how this approach
      predicts cervical stromal involvement, nodal and distant metastasis.

      The clinical importance of this project is answer the most relevant questions, i.e.,
      prediction of tumor involvement of myometrium, cervix, and lymph nodes. This will be
      important for understanding the background mechanism of changes identified by MR and
      18-F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) /PET, in order to develop novel
      imaging biomarkers or therapeutic targets. Both molecular imaging and metabolomics are
      complimentary and share similarities: (1) Comprehensive data representing the information of
      the living system as a whole (2) information rich data which reflecting the complexity of the
      biological system (3) ease for longitudinal observation. Metabolomics data provides more
      details on biochemistry whilst imaging data provides more spatial localization details. A
      combination of imaging and metabolomics approach would be an ideal tool to develop biomarkers
      for uterine malignancy. By completion of this project, the investigators expect the most
      important metabolic biomarkers will be established, and potentially serve as functional tools
      to guide therapy for patient with uterine malignancy.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients in a tertiary referral center.
      
Biospecimen description: 
      1. Plasma sample preparation for global metabolites analysis and lipidomic analysis:

        2. Urine samples will be diluted with distilled water. Samples are centrifuged at 14,000 g
           for 5 min, and the supernatants will be collected for LC-MS analysis.

        3. Cellular metabolites extraction: Extraction method will be carried out by the method
           modified by Munger and Patterson. The medium will be aspirated from culture plates
           containing cells and 80% methanol (at -80°C) will immediately be added.
    
Keywords: biomarker; cancer metabolism; chemical exchange saturation transfer; endometrial cancer; diffusion-weighted imaging; magnetic resonance spectroscopy; uterine malignancy