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

Author(s)

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 15, p. 16-pg., 2023-08-01.

Abstract

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)

• FAPESP's process: 13/23277-8 - Molecular aspects involved in the development and progression of breast ductal carcinoma: investigation of carcinoma in situ progression and the role of BRCA1 mutation in the triple negative tumor
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50943-1 - INCT 2014: on Oncogenomics and Therapeutic Inovations
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/04920-3 - Evaluation and molecular characterization of circulatong tumor cells of Ovarian Cancer patients
• Grantee: Anna Paula Carreta Ruano
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/18100-8 - Analysis of blood markers in patients with Osteosarcoma, Soft Tissue Sarcomas and Desmoid Tumor
• Grantee: Alexcia Camila Braun
• Support Opportunities: Scholarships in Brazil - Doctorate