Circulating endothelial cells and microparticles as diagnostic and prognostic biomarkers in small-cell lung cancer

Fadi Najjar; Moosheer Alammar; Ghassan Al-Massarani; Nissreen Almalla; Abdulmunim Japawe; Adnan Ikhtiar

doi:10.1016/j.lungcan.2018.06.033

Circulating endothelial cells and microparticles as diagnostic and prognostic biomarkers in small-cell lung cancer

Lung Cancer. 2018 Oct:124:23-30. doi: 10.1016/j.lungcan.2018.06.033. Epub 2018 Jul 21.

Authors

Fadi Najjar¹, Moosheer Alammar², Ghassan Al-Massarani³, Nissreen Almalla³, Abdulmunim Japawe⁴, Adnan Ikhtiar⁴

Affiliations

¹ Biomarkers Laboratory, Radiation Medicine Department, Atomic Energy Commission of Syria (AECS), 17 Nissan Street, P.O. Box 6091, Damascus, Syria. Electronic address: ascientific29@aec.org.sy.
² Division of Thoracic Oncology, Oncology Department, Albairouni University Hospital, Hall 2 (A 30/3), Homs Harasta Road, Damascus, Syria.
³ Biomarkers Laboratory, Radiation Medicine Department, Atomic Energy Commission of Syria (AECS), 17 Nissan Street, P.O. Box 6091, Damascus, Syria.
⁴ Radiobiology Laboratory, Biotechnology Department, Atomic Energy Commission of Syria (AECS), 17 Nissan Street, P.O. Box 6091, Damascus, Syria.

PMID: 30268466
DOI: 10.1016/j.lungcan.2018.06.033

Abstract

Objectives: It has been proposed that circulating endothelial cells (CECs) and microparticles (MPs) may be useful for the assessment of patients with non-small-cell lung cancer (NSCLC). However, little is known about the potential clinical relevance of these biomarkers in small-cell lung cancer (SCLC). Therefore, we investigated the utility of baseline levels of CECs and MPs in SCLC patients.

Materials and methods: An immunomagnetic separation (IMS) technique was used to isolate and quantify CECs in the peripheral blood, while plasma samples were analyzed using flow cytometry for the measurement of circulating MPs.

Results: We prospectively collected data from 56 patients and 41 healthy individuals. Forty-three patients presented at initial diagnosis and 13 patients presented at relapse. Baseline levels of CECs and MPs were significantly higher in SCLC patients either at initial diagnosis or at relapse than in healthy subjects (p < 0.0002 and p < 0.007, respectively). However, estimated tumor volume (ETV) was significantly correlated with basal MP values (p < 0.0001) but not with pretreatment CECs (p = 0.57). The amount of baseline CECs and MPs was significantly lower in patients with an objective response (OR, n = 23) than in those with progressive disease (PD, n = 15) after treatment (p = 0.016 and 0.05, respectively). With cut-off values of 110 cells/mL for CECs and 1257 events/μL for MPs according to receiver operating characteristics (ROC) analysis, baseline levels of these biomarkers were not significantly correlated with either progression-free survival (PFS) or overall survival (OS). However, patients with 6-month PFS displayed significantly decreased pretreatment CEC counts (p = 0.042), whereas basal MP values significantly increased in 1-year survivors compared with those in non-survivors (p = 0.05).

Conclusion: Our results suggest that baseline CECs and MPs may be predictive biomarkers of tumor response and long-term survival in SCLC patients.

Keywords: Biomarkers; Circulating endothelial cells; Clinical outcome; Microparticles; Small-cell lung cancer.

MeSH terms

Adult
Aged
Blood Circulation
Carcinoma, Small Cell / diagnosis*
Carcinoma, Small Cell / mortality
Cell-Derived Microparticles / pathology*
Endothelial Cells / pathology*
Female
Follow-Up Studies
Humans
Immunomagnetic Separation
Lung Neoplasms / diagnosis*
Lung Neoplasms / mortality
Male
Middle Aged
Predictive Value of Tests
Prognosis
Prospective Studies
Survival Analysis