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Case Report

A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation

1
Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK
2
Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK
3
Centre for Tumour Biology, Barts Cancer Institute—A CRUK Centre of Excellence, Queen Mary University of London, London EC1M 5PZ, UK
4
Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London EC1M 5PZ, UK
5
Barts Pancreas Tissue Bank, Barts Cancer Institute—A CRUK Centre of Excellence, Queen Mary University London, London EC1M 5PZ, UK
6
Centre for Global Oncology, Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Curr. Oncol. 2022, 29(10), 6754-6763; https://doi.org/10.3390/curroncol29100531
Received: 25 July 2022 / Revised: 7 September 2022 / Accepted: 14 September 2022 / Published: 21 September 2022
(This article belongs to the Section Surgical Oncology)
Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for the assessment of treatment response poses a challenge for validating novel therapies. In this case study, we evaluate the feasibility of collecting endoscopic ultrasound (EUS)-guided longitudinal fine-needle aspiration biopsies (FNABs) from two PDAC patients and conduct gene expression studies associated with tumour microenvironment changes associated with radiofrequency ablation (RFA). Methods: EUS-guided serial/longitudinal FNABs of tumour were collected before and after treatment from two stage III inoperable gemcitabine-treated PDAC patients treated with targeted RFA three times. Biopsies were analysed using a custom NanoString panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes and immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. Results: Two-course RFA led to the upregulation of the CD1E gene (involved in antigen presentation) in both patients 1 and 2 (4.5 and 3.9-fold changes) compared to baseline. Patient 1 showed increased T cell genes (CD4—8.7-fold change, CD8—35.7-fold change), cytolytic function (6.4-fold change) and inflammatory response (8-fold change). A greater than 2-fold upregulation of immune checkpoint genes was observed post-second RFA in both patients. Further, two-course RFA led to increased PDGFRα (4.5-fold change) and CAF subtypes B and C genes in patient 1 and subtypes A, B and D genes in patient 2. Patient 2-derived CAFs post-first RFA showed expression of PDGFRα, POSTN and MYH11 proteins. Finally, RFA led to the downregulation of classical PDAC subtype-specific genes in both patients. Conclusions: This case study suggests longitudinal EUS-FNAB as a potential resource to study tumour and microenvironmental changes associated with RFA treatment. A large sample size is required in the future to assess the efficacy and safety of the treatment and perform comprehensive statistical analysis of EUS-RFA-based molecular changes in PDAC. View Full-Text
Keywords: fine-needle aspiration biopsy; pancreatic ductal adenocarcinoma; tumour microenvironment; immune checkpoint genes; radiofrequency ablation fine-needle aspiration biopsy; pancreatic ductal adenocarcinoma; tumour microenvironment; immune checkpoint genes; radiofrequency ablation
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MDPI and ACS Style

Lawrence, P.V.; Desai, K.; Wadsworth, C.; Mangal, N.; Kocher, H.M.; Habib, N.; Sadanandam, A.; Sodergren, M.H. A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation. Curr. Oncol. 2022, 29, 6754-6763. https://doi.org/10.3390/curroncol29100531

AMA Style

Lawrence PV, Desai K, Wadsworth C, Mangal N, Kocher HM, Habib N, Sadanandam A, Sodergren MH. A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation. Current Oncology. 2022; 29(10):6754-6763. https://doi.org/10.3390/curroncol29100531

Chicago/Turabian Style

Lawrence, Patrick V., Krisha Desai, Christopher Wadsworth, Nagina Mangal, Hemant M. Kocher, Nagy Habib, Anguraj Sadanandam, and Mikael H. Sodergren. 2022. "A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation" Current Oncology 29, no. 10: 6754-6763. https://doi.org/10.3390/curroncol29100531

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