An Exploratory Analysis of Changes in Circulating Plasma Protein Profiles Following Image-Guided Ablation of Renal Tumours Provides Evidence for Effects on Multiple Biological Processes.
Tze Min WahJim ZhongMichelle WilsonNaveen S VasudevRosamonde E BanksPublished in: Cancers (2021)
Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic effects and provide insight into impact both on the tumour and immune system. Patients undergoing cryotherapy (CRYO), radiofrequency ablation (RFA) or microwave ablation (MWA) for small renal tumours were recruited. Blood samples were obtained at four timepoints; two baselines prior to IGA and at 24 h and 1-3 months post-IGA, and a panel of 164 proteins measured. Of 55 patients recruited, 35 underwent ablation (25 CRYO, 8 RFA, 2 MWA) and biomarker measurements. The most marked changes were 24 h post-CRYO, with 29 proteins increasing and 18 decreasing significantly, principally cytokines and proteins involved in regulating inflammation, danger-associated molecular patterns (DAMPs), cell proliferation, hypoxic response, apoptosis and migration. Intra-individual variation was low but inter-individual variation was apparent, for example all patients showed increases in IL-6 (1.7 to 29-fold) but only 50% in CD27. Functional annotation analysis highlighted immune/inflammation and cell proliferation/angiogenesis-related clusters, with interaction networks around IL-6, IL-10, VEGF-A and several chemokines. Increases in IL-8, IL-6, and CCL23 correlated with cryoprobe number (p = 0.01, rs = 0.546; p = 0.009, rs = 0.5515; p = 0.005, rs = 0.5873, respectively). This initial data provide further insights into ablation-induced biological changes of relevance in informing trial design of immunotherapies combined with ablation.
Keyphrases
- radiofrequency ablation
- cell proliferation
- end stage renal disease
- oxidative stress
- patients undergoing
- newly diagnosed
- chronic kidney disease
- high resolution
- ejection fraction
- peritoneal dialysis
- clinical trial
- catheter ablation
- vascular endothelial growth factor
- study protocol
- endothelial cells
- computed tomography
- magnetic resonance imaging
- signaling pathway
- protein protein
- machine learning
- rna seq
- electron microscopy
- single cell
- liver fibrosis
- electronic health record
- deep learning
- mass spectrometry
- contrast enhanced ultrasound
- atrial fibrillation
- patient reported