1 / 20

ProstOmics ‘Tissue is the issue’: a multi- omics approach to improve pros t ate cancer diagnosis

ERCStG2017 ProstOmics Tessem. ProstOmics ‘Tissue is the issue’: a multi- omics approach to improve pros t ate cancer diagnosis. PI : May-Britt Tessem Associate Professor/ R esearch S cientist Department of Circulation and Medical Imaging NTNU, Trondheim. The prostate

hnaomi
Download Presentation

ProstOmics ‘Tissue is the issue’: a multi- omics approach to improve pros t ate cancer diagnosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ERCStG2017 ProstOmics Tessem ProstOmics ‘Tissue is the issue’: a multi-omicsapproach to improve prostate cancer diagnosis PI: May-Britt Tessem Associate Professor/Research Scientist Department ofCirculation and Medical Imaging NTNU, Trondheim

  2. The prostate cancer challenge • most common cancer in men • Diagnosis is challenging • good clinical tools are limited Underdiagnosis Overdiagnosis Treatment side-effects Life threatening? Identify the life threatening prostate cancers

  3. How to obtainthecorrectdiagnosis? Reliable biomarkers multi-level information on molecular signatures of each cancer patient Uniqueresources: High qualitylarge-scaletissuebiobanks Key idea: multi-omicstechnology and histopathologyonthe same prostatetissue sample

  4. Human tissuebiobanks available for ERC project 1: ProstatectomybiopsiesN=1000 2: ProstatectomytissueslicesN~1000 3: MR guidedbiopsies N=100 All material approved by the Regional EthicsCommitte and collectedafterinformedconsent

  5. My work: biomarkers for aggressive prostate cancer Basis for ERC project Giskeødegård et al. Plos One 2011 Bertilsson et al. Clin Cancer Res 2011 First integration of metabolomics and transcriptomics Citrate and spermine (polyamine) MR markers of aggressiveness In vivo detection Selnæs et al Invest. Radiol. 2012 Braadland et al. Accepted BJC MR spectroscopic imaging (MRSI) Recurrence (citrate and polyamine)

  6. Key methodology and collaborations Matrix-Assisted Laser Desorption Ionization Prof. Dr. Uwe Karst University of MuensterInstitute of Inorganic andAnalytical Chemistry, Germany Laser Ablation Inductively Coupled Plasma Mass Spectrometry imaging Genomics Core Facility Pathologist/Assoc. Professor Elin Richardsen Department of Medical Biology, Tromsø Cellular and Molecular Imaging Core Facility (CMIC)

  7. Overall projectaims • to improve diagnostic and prognostic accuracy of prostate cancer by novel and promising biomarkers • To validate their clinical potential and their connection to heterogeneity.

  8. May-Britt Tessem -CV highlights Communicating science • 24 international publications • 7 last authorpublications • High ranked journals: ClinCanRes, British Journal Cancer, Cancer Res. • Supervising 5 PhDcandidates (main supervisor for 3) Prostate cancer patientuser panel: #NTNUmedicine | blog ERC funding: Ambitious research program to improve prostate cancer diagnostics

  9. WP1: Implementationofthemulti-omicsprotocol onthesame prostatetissue sample

  10. Aim 1: Detectmetabolite biomarkers for aggressive/recurrentprostate cancer by high speed MALDI-Imaging (N=1000 needlebiopsies, N=100 MR guidedbiopsies) MALDI of spermine in a prostate biopsy (preliminary result from my lab) ExpectedOutcome: Novelmetabolic MALDI biomarkers withprognosticvalue

  11. Aim 2: Assestissueheterogeneity by spatial MALDI markers 1) tissue sample (stroma-, epithelial-, cancer cells) 2) tumor/multifocal tumors 3) normal appearingtissueclose to tumors (cancer fieldeffects) N=100 whole mount slices, n~600 samples Expected outcome: Novel MALDI biomarkers for specific cell types and tissue structures

  12. https://www.ntnu.edu/mh/mr-corefacility WP 2: Validate and assessmechanismsof Citrate, zinc and polyamines

  13. Aim 3: Evaluatetheclinicalpotentialoftargeted MR guidedbiopsies (MRGB) compared to in vivo MRSI onthe same patients Expected outcome: Citrate and spermine are proven useful prognostic markers in MRGB tissue and in MRSI Biopsy taken within the MR magnet First of its kind- MR spectrum of a MRGB (~3mg) (preliminary data from my group).

  14. WP 3: Metabolism and immune responses in prostate cancer Aim: To determineifinflammatoryresponses(IL-1β)account for alterations in succinate and citrate in human prostatetissue. Mills et al. Cell 2016 Expectedoutcome: Metabolism is linked to inflammatoryresponses newpossibilities for immune therapy in prostate cancer

  15. Human tissuebiobanks available for ERC project My biobankwork New harvesting method Bertilsson et al. Prostate 2011 Tessem et al. Magn. Res. Med. 2008

  16. How to obtainthecorrectdiagnosis? 12-15 transrectalultrasound (TRUS)- guidedbiopsies Grade Group system 1-5 Not sufficient to distinguish life threatening from indolent prostate cancer

  17. Heterogeneity (between-, withinpatients, in tissuecomposition) Real life! = = Shift focus away from cell lines towards large-scale human tissue cohorts Cell line

  18. Aim 1: Validatecitrate, spermine and zincwith MR spectroscopy and MS imaging to evaluatetheclinicalpotential as prognostic markers (N=1000 needlebiopsies, N=100 MR guidedbiopsies) Aim 2: To determineinfluenceofheterogeneity and underlying molecularmechanisms N=100 whole mount slices, n~600 samples Expected outcome: Validated tissue-specific metabolite biomarkers proven useful for the clinic

  19. High risk - highgain- impact • High risk: • biomarkers not strong enough after validation • High gain: • Novel and validated biomarkers • Novel understanding of molecular pathways • Novel understanding of heterogeneity • Strong clinical potential - in vivo data • Impact: • Patients receive the correct diagnosis and better care

More Related