The Potential of Folate-Positive Circulating Tumor Cells (FR+-CTC) as a Novel Diagnostic Biomarker for Non-Small Cell Lung Cancer A Systematic Review of Clinical Trials

Main Article Content

Garry Soloan
Mr
Ms.

Abstract

Abstract


Background: Non-small-cell lung cancer (NSCLC) is malignancy that remains the leading cause for cancer mortalities. Diagnosis is often made in advanced stages, hence, the unmet need for novel diagnostic methods. FR+-CTC is acknowledged as a potential diagnostic biomarker that detects NSCLC presence, distinguishing it from benign lung diseases and healthy individuals.


Purpose of Study: This study aims to investigate the potential of FR+-CTC to be utilized as an accurate, sensitive, and specific diagnostic biomarker for NSCLC.


Methods: This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Studies were obtained from databases namely Wiley Online Library, MEDLINE, Science Direct, CENTRAL, and ProQuest. The outcome assessed includes summary receiver operating characteristics (sROC) evaluating diagnostic accuracy taking form of area under the curve (AUC) analysis. Risk of bias assessment is carried out using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2).


Results: 5 studies confirm a higher amount of FR+-CTC in peripheral blood can be utilized as a diagnostic marker in NSCLC patients. Detection of FR+CTC in NSCLC diagnosis is superior to existing biomarkers with a sensitivity and specificity of 81.94% and 73.08%. FR+CTC presents the highest AUC (0.823; 95% CI, 0.773-0.874) compared to other biomarkers. FR +- CTC levels can differentiate the types of lung adenocarcinoma with acceptable sensitivity. 

Conclusion: FR+-CTC detection is a reliable diagnostic method with the highest degree of accuracy for diagnosing NSCLC compared to other biomarkers. FR+-CTC can also be utilized to predict possible malignancies, even in its early stages.


 


Keywords: Biomarkers, circulating tumor cells, diagnosis, folate receptor, lung cancer, NSCLC


 

Article Details

How to Cite
Soloan, G., Ivan Sini, K. P. . and Meutia Abubakar, R. Z. (2023) “The Potential of Folate-Positive Circulating Tumor Cells (FR+-CTC) as a Novel Diagnostic Biomarker for Non-Small Cell Lung Cancer: A Systematic Review of Clinical Trials”, Journal of Asian Medical Students’ Association. Kuala Lumpur, Malaysia, 10(1). Available at: https://jamsa.amsa-international.org/index.php/main/article/view/405 (Accessed: 21May2024).
Section
Review Articles

References

Sadate A, Occean BV, Beregi JP, Hamard A, Addala T, de Forges H, Fabbro-Peray P, Frandon J. Systematic review and meta-analysis on the impact of lung cancer screening by low-dose computed tomography. European Journal of Cancer. 2020 Jul 1;134:107-14.

Toumazis I, Bastani M, Han SS, Plevritis SK. Risk-Based lung cancer screening: A systematic review. Lung Cancer. 2020 Jul 12.

Duma N, Santana-Davila R, Molina JR. Non–small cell lung cancer: epidemiology, screening, diagnosis, and treatment. InMayo Clinic Proceedings 2019 Aug 1 (Vol. 94, No. 8, pp. 1623-1640). Elsevier.

Chen X, Zhou F, Li X, Yang G, Zhang L, Ren S, et al. Folate receptor–positive circulating tumor cell detected by LT-PCR–based method as a diagnostic biomarker for non–small-cell lung cancer. Journal of thoracic oncology. 2015 Aug 1;10(8):1163-71.

Ding C, Zhou X, Xu C, Chen J, Ju S, Chen T, et al. Circulating tumor cell levels and carcinoembryonic antigen: An improved diagnostic method for lung adenocarcinoma. Thoracic cancer. 2018 Nov;9(11):1413-20.

Xue Y, Cong W, Xie S, Shu J, Feng G, Gao H. Folate-receptor-positive circulating tumor cells as an efficacious biomarker for the diagnosis of small pulmonary nodules. Journal of cancer research and therapeutics. 2018 Oct 1;14(7):1620.

Yu Y, Chen Z, Dong J, Wei P, Hu R, Zhou C, et al. Folate receptor-positive circulating tumor cells as a novel diagnostic biomarker in non-small cell lung cancer. Translational oncology. 2013 Dec 1;6(6):697-702.

Zhou Q, Geng Q, Wang L, Huang J, Liao M, Li Y, et al. Value of folate receptor-positive circulating tumour cells in the clinical management of indeterminate lung nodules: A non-invasive biomarker for predicting malignancy and tumour invasiveness. EBioMedicine. 2019 Mar 1;41:236-43.

Heineman DJ, Daniels JM, Schreurs WH. Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy. Therapeutic advances in medical oncology. 2017 Sep;9(9):599-609.

Brown NA, Aisner DL, Oxnard GR. Precision Medicine in Non–Small Cell Lung Cancer: Current Standards in Pathology and Biomarker Interpretation. American Society of Clinical Oncology Educational Book. 2018 May 23;38:708-15.

Detterbeck FC. The eighth edition TNM stage classification for lung cancer: what does it mean on main street?. The Journal of thoracic and cardiovascular surgery. 2017 Sep 28;155(1):356-9.

Li N, Zhong D, Chen H, Huang T, Hou P, Zhang Y, et al. The utility of folate receptor-positive circulating tumor cell in cancer diagnosis in the elderly population. Cancer management and research. 2019;11:4097.

Akpe V, Kim TH, Brown CL, Cock IE. Circulating tumour cells: a broad perspective. Journal of the Royal Society Interface. 2020 Jul 29;17(168):20200065.

Thomas A, Maltzman J, Hassan R. Farletuzumab in lung cancer. Lung Cancer. 2013 Apr 1;80(1):15-8.

Kapeleris J, Kulasinghe A, Warkiani M, Vela I, Kenny L, O'Byrne K et al. The prognostic role of circulating tumor cells (CTCs) in lung cancer. Frontiers in Oncology. 2018;8.

Hanssen A, Loges S, Pantel K, Wikman H. Detection of circulating tumor cells in non-small cell lung cancer. Frontiers in Oncology. 2015;5.