Tumoral exosomes profile in metastatic pancreatic adenocarcinoma patients during chemotherapy treatment / Nuno Miguel Reis Couto ; orient. Bruno Costa-Silva
Main Author Couto, Nuno Miguel Reis Secondary Author Costa-Silva, Bruno Language Inglês. Country Portugal. Publication Lisboa : NOVA Medical School, Universidade NOVA de Lisboa, 2023 Description 239 p. Dissertation Note or Thesis: Tese de DoutoramentoMedicina
2023
Faculdade de Ciências Médicas, Universidade NOVA de Lisboa
Abstract Abstract Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second-leading cause of cancer deaths by 2030. This is related to the incidence increment, latter diagnosis, and absence of therapies with efficacy. Imaging techniques are the standard for monitoring the therapy response in PDAC, but these techniques have considerable limits, including delayed disease progression detection and difficulty in distinguishing benign from malignant lesions. The use of CA19.9 as tumor marker is validated in clinical, but also present some limitations (is not expressed in up to 20% of patients and can be increased in several benign conditions including biliary tree complications). The study of new biomarkers, especially with the use of technologies associated with liquid biopsies, has been used to try to solve the limitations. Extracellular vesicle (EV) liquid biopsy is an emerging diagnosis modality. Still, most research on EV-based diagnosis is based on point analyses of EVs at certain times. Longitudinal studies of EV populations before and during therapeutic interventions are still largely unexplored. We analyzed plasma EV protein composition at diagnosis and throughout PDAC therapy using mass spectrometry (MS). Using flow cytometry, we validated the previous result and explored the evolution of the population of EVs expressing the identified protein in MS in patients with metastatic PDAC in accordance with the chemotherapy treatment results. We found that IgG is linked to the diagnosis of PDAC and the patient’s response to therapy, and that IgG+ EV population increases with disease progression and reduces with treatment response. Importantly, this covers PDAC patients devoid of the standard PDAC serum marker CA19.9 expression. We also observed that IgG is bound to EVs via the tumor antigen MAGE B1, and that this is independent of the patient’s inflammatory condition and IgG serum levels. With these results, we propose that a population analysis of IgG+ EVs in PDAC plasma could represent a novel method to supplement the monitoring of the treatment response of patients with metastatic PDAC Topical name Extracellular Vesicles
Biomarkers
Academic Dissertation Online Resources Click here to access the eletronic resource http://hdl.handle.net/10362/155202
| Item type | Current location | Call number | url | Status | Date due | Barcode |
|---|---|---|---|---|---|---|
| Documento Eletrónico | Biblioteca NMS|FCM online | RUN | 155202 | Available | 20230094 |
Tese de Doutoramento Medicina 2023 Faculdade de Ciências Médicas, Universidade NOVA de Lisboa
Abstract Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second-leading cause of cancer deaths by 2030. This is related to the incidence increment, latter diagnosis, and absence of therapies with efficacy. Imaging techniques are the standard for monitoring the therapy response in PDAC, but these techniques have considerable limits, including delayed disease progression detection and difficulty in distinguishing benign from malignant lesions. The use of CA19.9 as tumor marker is validated in clinical, but also present some limitations (is not expressed in up to 20% of patients and can be increased in several benign conditions including biliary tree complications). The study of new biomarkers, especially with the use of technologies associated with liquid biopsies, has been used to try to solve the limitations. Extracellular vesicle (EV) liquid biopsy is an emerging diagnosis modality. Still, most research on EV-based diagnosis is based on point analyses of EVs at certain times. Longitudinal studies of EV populations before and during therapeutic interventions are still largely unexplored. We analyzed plasma EV protein composition at diagnosis and throughout PDAC therapy using mass spectrometry (MS). Using flow cytometry, we validated the previous result and explored the evolution of the population of EVs expressing the identified protein in MS in patients with metastatic PDAC in accordance with the chemotherapy treatment results. We found that IgG is linked to the diagnosis of PDAC and the patient’s response to therapy, and that IgG+ EV population increases with disease progression and reduces with treatment response. Importantly, this covers PDAC patients devoid of the standard PDAC serum marker CA19.9 expression. We also observed that IgG is bound to EVs via the tumor antigen MAGE B1, and that this is independent of the patient’s inflammatory condition and IgG serum levels. With these results, we propose that a population analysis of IgG+ EVs in PDAC plasma could represent a novel method to supplement the monitoring of the treatment response of patients with metastatic PDAC
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