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

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Garry Soloan



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


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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: (Accessed: 21May2024).
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