The utility of folate receptor-positive circulating tumor cell in cancer diagnosis in the elderly population

Abstract

Purpose: Cancer mortality is relatively high in the elderly population. Folate receptor-positive circulating tumor cell (FR+CTC) has proven an effective biomarker for diagnosis of lung cancer and bladder cancer and may be suitable for other cancer types accompanied with a high expression of FR. To date, the diagnostic efficiency of FR+CTC in the elderly population has not been systematically studied. Herein, we sought to investigate the utility of FR+CTC in cancer diagnosis in the elderly population and the influence of comorbidities on FR+CTC levels in such a population. Patients and methods: A total of 35 cancer patients (including 23 lung cancers, 8 colorectal cancers, and 4 other cancers) and 40 noncancer participants, aged between 80 and 110, were recruited in this study. Three milliliters of pretreatment peripheral blood was collected from each participant for FR+CTC analysis. Results: Compared to previous studies, the FR+CTC level was slightly higher in the elderly population (median FR+CTC levels in cancer patients versus noncancer participants were 14.3 versus 9.2 CTC U/3 mL, respectively, P=0.0002). With 10.0 CTC U/3 mL as the cut-off value, the sensitivity and specificity of FR+CTC were 85.7% and 65.0%, respectively. In combination with established serum tumor biomarkers, the diagnostic efficiency of FR+CTC further improved (sensitivity=87.9%, specificity=71.8%). Clinical factors including diabetes, cardiovascular diseases, respiratory diseases, cerebral infarction, and cardiac, liver, and kidney function were not associated with the FR+CTC level (P>0.05). Conclusion: In this exploratory study, we showed that FR+CTC is an effective biomarker for cancer diagnosis in the elderly population. The presence of comorbidities did not affect the diagnostic efficiency of FR+CTC.

Keywords: biomarker; cancer; circulating tumor cell; elderly; folate receptor.

Figure 1

FR+CTC levels. The box-and-whisker plot showing the median and IQR of FR+CTC levels in patients with lung cancers, colorectal cancers, prostate cancers, pancreatic cancers, lymphoma, and noncancer participants. Abbreviation: FR+CTC, folate receptor-positive circulating tumor cell; IQR, interquartile range.

Figure 2

Diagnostic value of FR+CTCs. ROC curve for FR+CTC, CA125, CA199, CEA, CYFRA21-1, CA724, and NSE in discriminating patients with noncancer participants from patients with (A) lung cancers; (B) colorectal cancers; and (C) all cancers. Notes: Red line indicates FR+CTC; orange line indicates CA125; yellow line indicates CA19-9; green line indicates CEA; blue line indicates CYFRA21-1; dotted black line indicates CA724; purple line indicates NSE. Abbreviations: CRC, colorectal cancer; FR+CTC, folate receptor-positive circulating tumor cell; ROC, receiver operating characteristic; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment antigen; NSE, neuron-specific enolase.

Figure 3

Diagnostic value of FR+CTC combined with tumor marker. ROC curve for FR+CTC combined with tumor marker in discriminating noncancer participants from patients with (A) lung cancers and (B) all cancers. CYFRA21-1, CA724, and NSE tests had not performed for the lymphoma patient; thus, this patient was excluded from this analysis. Abbreviation: FR+CTC, folate receptor-positive circulating tumor cell; CA, carbohydrate antigen; CYFRA21-1, cytokeratin 19 fragment antigen; NSE, neuron-specific enolase; ROC, receiver operating characteristic.