dc.contributor.author | Lawrence, PV | |
dc.contributor.author | Desai, K | |
dc.contributor.author | Wadsworth, C | |
dc.contributor.author | Mangal, N | |
dc.contributor.author | Kocher, HM | |
dc.contributor.author | Habib, N | |
dc.contributor.author | Sadanandam, A | |
dc.contributor.author | Sodergren, MH | |
dc.coverage.spatial | Switzerland | |
dc.date.accessioned | 2022-12-20T11:56:05Z | |
dc.date.available | 2022-12-20T11:56:05Z | |
dc.date.issued | 2022-09-21 | |
dc.identifier | curroncol29100531 | |
dc.identifier.citation | Current Oncology, 2022, 29 (10), pp. 6754 - 6763 | |
dc.identifier.issn | 1198-0052 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5610 | |
dc.identifier.eissn | 1718-7729 | |
dc.identifier.eissn | 1718-7729 | |
dc.identifier.doi | 10.3390/curroncol29100531 | |
dc.description.abstract | 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. | |
dc.format | Electronic | |
dc.format.extent | 6754 - 6763 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI | |
dc.relation.ispartof | Current Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | fine-needle aspiration biopsy | |
dc.subject | immune checkpoint genes | |
dc.subject | pancreatic ductal adenocarcinoma | |
dc.subject | radiofrequency ablation | |
dc.subject | tumour microenvironment | |
dc.subject | Humans | |
dc.subject | Tumor Microenvironment | |
dc.subject | Receptor, Platelet-Derived Growth Factor alpha | |
dc.subject | Pancreatic Neoplasms | |
dc.subject | Carcinoma, Pancreatic Ductal | |
dc.subject | Radiofrequency Ablation | |
dc.subject | Biopsy | |
dc.subject | Ultrasonography, Interventional | |
dc.subject | Gene Expression | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-09-14 | |
dc.date.updated | 2022-12-20T11:55:04Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.3390/curroncol29100531 | |
rioxxterms.licenseref.startdate | 2022-09-21 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36290808 | |
pubs.issue | 10 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.3390/curroncol29100531 | |
pubs.volume | 29 | |
icr.researchteam | Systems - Precision Med | |
dc.contributor.icrauthor | Sadanandam, Anguraj | |
icr.provenance | Deposited by Mr Arek Surman on 2022-12-20. Deposit type is initial. No. of files: 1. Files: A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from .pdf | |