Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Area
2.2. Study Subjects and Sample Collection
2.3. Determination of Biomarker Serum Levels
2.4. Statistical Analyses
3. Results
3.1. Characteristics of the Participants
3.2. Comparative Serum Analyte Levels in LC Versus HC Groups
3.3. Comparative Levels of Serum Analytes Among LC, LR, and HR Groups
3.4. Evaluation of the Diagnostic Capability of Serum Biomarkers for LC Risk in HC and HR Groups
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AUC | Area under the curve |
CEA | Carcinoembryonic antigen |
CI | Confidence interval |
CYFRA 21-1 | Cytokeratin 19 fragment |
HC | Healthy controls |
HR | High radon |
IDO-1 | Indoleamine 2,3-dioxygenase 1 |
IL-6 | Interleukin-6 |
IL-8 | Interleukin-8 |
LC | Lung cancer |
LDCT | Low-dose computed tomography |
LOD | Limit of detection |
LR | Low radon |
NSCLC | Non-small cell lung cancer |
PM | Particulate matter |
ROC | Receiver operating characteristic |
SCLC | Small cell lung cancer |
SD | Standard deviation |
TGF-alpha | Transforming growth factor alpha |
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Characteristics | LC (n = 15) | LR (n = 15) | HR (n = 15) | p Value |
---|---|---|---|---|
Age in years, Mean (SD) | 62 (13.3) | 61.1 (11.2) | 61.3 (13) | 0.98 |
Gender | 1 | |||
Male | 8 | 8 | 8 | |
Female | 7 | 7 | 7 | |
Education | 0.91 | |||
Middle school or lower | 9 | 10 | 9 | |
High school or higher | 6 | 5 | 6 | |
Alcohol consumption | 0.84 | |||
Yes | 2 | 3 | 2 | |
No | 13 | 12 | 13 | |
Smoking status | 0.004 | |||
Never smokers | 10 | 15 | 15 | |
Former smokers | 5 | 0 | 0 | |
Stage of lung cancer | - | |||
I | 13 | 0 | 0 | |
II | 2 | 0 | 0 | |
Tumor histology | - | |||
Adenocarcinoma | 10 | 0 | 0 | |
Squamous cell carcinoma | 5 | 0 | 0 |
Markers (pg/mL) | LC (n = 15) | HC (n = 30) | LR (n = 15) | HR (n = 15) |
---|---|---|---|---|
CYFRA 21-1 | ||||
Mean | 5325.8 | 1132.5 | 752 | 1513.1 |
SD | 16,631.1 | 766.2 | 470.5 | 827.3 |
Min | 274.9 | 274.9 | 274.9 | 346.4 |
Max | 65,353.5 | 3151.4 | 1321 | 3151.4 |
Median | 778.1 | 876.4 | 609 | 1392.7 |
CEA | ||||
Mean | 3990 | 459.8 | 391.7 | 527.9 |
SD | 7882.8 | 312.6 | 305.6 | 314.8 |
Min | 121.2 | 62.2 | 62.2 | 107.6 |
Max | 29,384.8 | 1174.9 | 1010.2 | 1174.9 |
Median | 568.8 | 377.7 | 316.6 | 572.6 |
IL-6 | ||||
Mean | 2.2 | 0.7 | 0.5 | 0.9 |
SD | 2.4 | 0.7 | 0.4 | 1 |
Min | 0.5 | 0.1 | 0.1 | 0.1 |
Max | 8.8 | 3 | 1.2 | 3 |
Median | 1.4 | 0.3 | 0.3 | 0.3 |
IL-8 | ||||
Mean | 14.2 | 5.9 | 5.7 | 6.1 |
SD | 14.2 | 2.7 | 2.6 | 2.8 |
Min | 2.7 | 2.1 | 2.1 | 2.3 |
Max | 43.1 | 13.1 | 11.8 | 13.1 |
Median | 6.8 | 5.5 | 5.4 | 5.9 |
TGF-alpha | ||||
Mean | 8.5 | 8.3 | 7.4 | 9.2 |
SD | 10.5 | 6.5 | 7.7 | 5.2 |
Min | 1 | 0.8 | 0.8 | 4.4 |
Max | 42.9 | 32.1 | 32.1 | 18.9 |
Median | 4.7 | 6.4 | 5.3 | 7.6 |
IDO-1 | ||||
Mean | 138.3 | 243.4 | 252.9 | 233.8 |
SD | 111.8 | 312.6 | 324.1 | 311.7 |
Min | 37.2 | 39.9 | 39.9 | 54.8 |
Max | 393.2 | 1248.1 | 1238.2 | 1248.1 |
Median | 115.4 | 143.4 | 149.8 | 118.4 |
Biomarkers | Cut-Off | AUC (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | Youden Index (95% CI) | p Value |
---|---|---|---|---|---|---|
CYFRA 21-1 | 1157.00 | 0.53 (0.35–0.72) | 0.40 (0.20–0.64) | 0.80 (0.63–0.90) | 0.20 (−0.17–0.55) | 0.72 |
CEA | 149.20 | 0.62 (0.43–0.80) | 0.20 (0.07–0.45) | 0.93 (0.79–0.98) | 0.13 (−0.14–0.43) | 0.20 |
IL-6 | 0.55 | 0.83 (0.70–0.96) | 0.62 (0.36–0.80) | 0.92 (0.79–0.98 | 0.53 (0.14–0.78) | 0.001 |
IL-8 | 4.90 | 0.68 (0.50–0.85) | 0.40 (0.20–0.64) | 0.87 (0.70–0.95) | 0.27 (−0.10–0.59) | 0.06 |
TGF-alpha | 10.31 | 0.58 (0.40–0.77) | 0.27 (0.11–0.52) | 0.87 (0.70–0.95) | 0.13 (−0.19–0.47) | 0.37 |
IDO-1 | 136.40 | 0.61 (0.43–0.79) | 0.53 (0.30–0.75) | 0.73 (0.56–0.86) | 0.27 (−0.14–0.61) | 0.24 |
IL-6 + IL-8 | 0.87 (0.76–0.99) | 0.41 (0.20–0.64) | 0.96 (0.83–0.99) | 0.37 (0.03–0.64) | 0.0003 |
Biomarkers | Cut-Off | AUC (95% CI) | Sensitivity (95% CI) | Specificity (95% CI) | Youden Index (95% CI) | p Value |
---|---|---|---|---|---|---|
CYFRA 21-1 | 1157.00 | 0.66 (0.45–0.87) | 0.67 (0.42–0.85) | 0.80 (0.55–0.93) | 0.47 (−0.03–0.78) | 0.13 |
CEA | 149.20 | 0.58 (0.37–0.79) | 0.20 (0.07–0.45) | 0.93 (0.70–0.99) | 0.13 (−0.23–0.44) | 0.47 |
IL-6 | 0.54 | 0.75 (0.55–0.95) | 0.54 (0.30–0.75) | 0.92 (0.70–0.99) | 0.46 (0.00–0.74) | 0.03 |
IL-8 | 4.54 | 0.64 (0.43–0.84) | 0.33 (0.15–0.58) | 0.87 (0.62–0.96) | 0.20 (−0.23–0.55) | 0.21 |
TGF-alpha | 10.31 | 0.67 (0.47–0.87) | 0.33 (0.15–0.58) | 0.87 (0.62–0.96) | 0.20 (−0.23–0.55) | 0.11 |
IDO-1 | 137.40 | 0.59 (0.38–0.79) | 0.47 (0.25–0.70) | 0.73 (0.48–0.89) | 0.20 (−0.27–0.59) | 0.42 |
CYFRA21-1 + IL-6 | 0.81 (0.63–0.99) | 0.75 (0.48–0.89) | 0.85 (0.62–0.96) | 0.60 (0.10–0.85) | 0.01 |
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Autsavapromporn, N.; Duangya, A.; Klunklin, P.; Chitapanarux, I.; Kranrod, C.; Jaikang, C.; Monum, T.; Tokonami, S. Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study. Biomedicines 2025, 13, 2145. https://doi.org/10.3390/biomedicines13092145
Autsavapromporn N, Duangya A, Klunklin P, Chitapanarux I, Kranrod C, Jaikang C, Monum T, Tokonami S. Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study. Biomedicines. 2025; 13(9):2145. https://doi.org/10.3390/biomedicines13092145
Chicago/Turabian StyleAutsavapromporn, Narongchai, Aphidet Duangya, Pitchayaponne Klunklin, Imjai Chitapanarux, Chutima Kranrod, Churdsak Jaikang, Tawachai Monum, and Shinji Tokonami. 2025. "Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study" Biomedicines 13, no. 9: 2145. https://doi.org/10.3390/biomedicines13092145
APA StyleAutsavapromporn, N., Duangya, A., Klunklin, P., Chitapanarux, I., Kranrod, C., Jaikang, C., Monum, T., & Tokonami, S. (2025). Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study. Biomedicines, 13(9), 2145. https://doi.org/10.3390/biomedicines13092145