Physical Poster + E-Poster Presentation 34th Lorne Cancer Conference 2022

Dual spatial assessment of contemporary patient pancreatic tumours via spatial transcriptomics and MALDI mass spectrometry imaging (#218)

Brooke Pereira 1 2 , Shona Ritchie 1 2 , David Herrmann 1 2 , Daniel Reed 1 2 , Cecilia Chambers 1 2 , Janett Stoehr 1 , Lea Abdulkhalek 1 , Joanna Skhinas 1 , Tatjana Schmitz 1 , Victoria Lee 1 , Max Nobis 1 2 , Xanthe Metcalf 1 , Amber Johns 1 , Ruth Lyons 1 , Gloria Jeong 1 , Lara Kenyon 1 , Angela Murphy 1 , Mehreen Ashri 1 , Kym Pham Stewart 3 , Australian Pancreatic Cancer Genome Initiative (APGI) 1 , Avner Australian Pancreatic Cancer Matrix Atlas (APMA) 1 , Lorraine Chantrill 1 4 , Jeff Evans 5 6 , Ben Parker 3 , Angus Grey 7 , Jennifer Morton 5 6 , Marina Pajic 1 2 , Sean Grimmond 3 , Jaswinder Samra 8 , Thomas Cox 1 2 , Anthony Gill 8 9 , Paul Timpson 1 2
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
  3. The University of Melbourne, Melbourne, VIC, Australia
  4. St Vincent’s Hospital, Sydney, NSW, Australia
  5. Beatson Institute, Cancer Research UK , Glasgow, Scotland, United Kingdom
  6. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
  7. Department of Physiology, The University of Auckland, Auckland, New Zealand
  8. Department of Surgery, Royal North Shore Hospital, St. Leonards, NSW, Australia
  9. NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St. Leonards, NSW, Australia

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, with a five-year survival rate of <10% [1]. PDAC is characterised by robust stromal activation, leading to extensive fibrosis (desmoplasia). Tissue changes are widespread, where extracellular matrix (ECM) proteins are not only aberrantly expressed and degraded, but also shift in terms of spatial organisation. Recently, we have shown that targeting desmoplasia can improve standard-of-care chemotherapy efficacy and impairs metastasis in PDAC mouse models [2-4]. As such, we have embarked on a new project to build a biobank of clinically relevant and diverse patient PDAC tumours with the aim to unravel their spatial signatures to discover new druggable targets.

To date, 16 fresh PDAC specimen sets (PDAC tumour, non-malignant pancreas, tumour/non-malignant interface, and duodenum/spleen) have been collected from Whipple’s procedures at Royal North Shore Hospital via the fibrosis-centric Avner Australian Pancreatic Cancer Matrix Atlas (APMA) group within the Australian Pancreatic Cancer Genome Initiative (APGI). This PDAC cohort is contemporary and unique as many patients received neoadjuvant chemotherapy such as Gemcitabine/Abraxane or FOLIFIRINOX prior to surgery, which is an emerging standard-of-care practice in the clinic. From the cohort, 14 tumour interface specimens from 13 patients were cryopreserved for spatial transcriptomics and MALDI-Mass Spectrometry imaging (MALDI-MSI) proteomics. Specimens were also collected for patient-derived xenografting (PDX), histopathology and genomic sequencing (ongoing). Overall, combining spatial proteomics with spatial transcriptomics will give us unparalleled information about the spatial signatures of PDAC tumours, which could reveal novel targets to treat this highly aggressive disease.

 

References

  1. Siegel, R.L., et al., CA: A Cancer Journal for Clinicians, 2021. 71(1): p. 7-33.
  2. Vennin, C., et al., Science Translational Medicine, 2017. 9(384): p. eaai8504.
  3. Vennin, C., et al., Nature Communications, 2019. 10(1): p. 3637.
  4. Murphy, K.J., et al., Science Advances, 2021. 7(40), eabh0363.