CD47 Expression in Circulating Tumor Cells and Circulating Tumor Microemboli from Non-Small Cell Lung Cancer Patients Is a Poor Prognosis Factor

Autor(es)

Torres, Jacqueline Aparecida ; Brito, Angelo Borsarelli Carvalho ; Silva, Virgilio Souza e ; Messias, Iara Monique ; Braun, Alexcia Camila ; Ruano, Anna Paula Carreta ; Buim, Marcilei E. C. ; Carraro, Dirce Maria ; Chinen, Ludmilla Thome Domingos

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 15, p. 16-pg., 2023-08-01.

Resumo

Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-beta/transforming growth factor-beta receptor type 1 (TGF-beta/TGF beta RI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the "don't eat me" signal to macrophages. Objectives: To isolate, quantify and analyze CTCs/CTMs from metastatic NSCLC patients, identify TGF beta RI/CD47 expression in CTCs/CTMs, and correlate with progression-free survival (PFS). Methods: Blood (10 mL) was collected at two time-points: T1 (before the beginning of any line of treatment; T2 (60 days after initial collection). CTCs were isolated using ISET & REG;. Immunocytochemistry was conducted to evaluate TGF beta RI/CD47 expression. Results: 45 patients were evaluated. CTCs were observed in 82.2% of patients at T1 (median: 1 CTC/mL; range: 0.33-11.33 CTCs/mL) and 94.5% at T2 (median: 1.33 CTC/mL; 0.33-9.67). CTMs were observed in 24.5% of patients and significantly associated with poor PFS (10 months vs. 17 months for those without clusters; p = 0.05) and disease progression (p = 0.017). CTMs CD47+ resulted in poor PFS (p = 0.041). TGF beta RI expression in CTCs/CTMs was not associated with PFS. Conclusion: In this study, we observed that CTC/CTM from NSCLC patients express the immune evasion markers TGF beta RI/CD47. The presence of CTMs CD47+ is associated with poor PFS. This was the first study to investigate CD47 expression in CTCs/CTM of patients with NSCLC and its association with poor PFS. (AU)

• Processo FAPESP: 13/23277-8 - Aspectos moleculares envolvidos no risco, desenvolvimento e progressão do carcinoma ductal de mama: busca de novos genes de susceptibilidade e investigação da progressão do carcinoma in situ e do papel da mutação em BRCA1 no tumor triplo negativo
• Beneficiário: Dirce Maria Carraro
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50943-1 - INCT 2014: de Oncogenômica e Inovação Terapêutica
• Beneficiário: Dirce Maria Carraro
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/04920-3 - Avaliação e caracterização molecular de células tumorais circulantes de pacientes com Câncer de Ovário
• Beneficiário: Anna Paula Carreta Ruano
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 19/18100-8 - Análise de marcadores sanguíneos em pacientes com Osteossarcoma, Sarcomas de Partes Moles e Tumor Desmóide
• Beneficiário: Alexcia Camila Braun
• Modalidade de apoio: Bolsas no Brasil - Doutorado