International Journal of Medical Science and Pharmaceutical Research

1–2 Despite advances in treatment strategies, lung tumors show clinical variability and traditional detection methods, involving imaging technologies (X-ray, CT scanning) or invasive tissue biopsy, which are far from perfect for early diagnosis and accurate prognosis of diseases. Thus, there is an increasing demand for non-invasive biomarkers that will enable early diagnosis and risk stratification. Circulating tumor DNA (ctDNA), a subset of cell-free DNA shed into the blood by tumor cells, is an attractive marker for representing tumour burden and molecular features. The purpose of the current study was to assess the diagnostic and prognostic significance of ctDNA in suspected lung tumor patients. Materials and Methods: This cross-sectional diagnostic study was carried out in Al-Forat Al-Awsat Oncology Center, Al-Najaf City-Iraq from March 2025 to September 2025. Seventy (70) patients with clinical and radiological suspicion of lung tumours were recruited. Peripheral blood samples obtained before final diagnostic studies. On the basis of histopathologic examination and/or chest computed tomography, 38 patients had lung tumors and 32 did not; these comprised control subjects. Serum levels of circulating tumor DNA were measured, blood carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE) were detected. ctDNA levels were significantly elevated in tumor-positive cases when compared to those that are negative (p < 0.002). The multivariate logistic regression analysis showed that ctDNA was an independent factor for lung cancer (p < 0.001). Receiver operating characteristic (ROC) curve analysis further verified the high diagnostic value of ctDNA, with an area under the curve (AUC) being 0.89, and sensitivity and specificity were 86.8% and 81.3%, respectively at an optimal cut-off value. It was concluded that circulating tumor DNA is an extremely informative non-invasive biomarker with significant diagnostic value and with prognostic impact in lung neoplasms. The ketone body ability of differentiation in conjunction with conventional tumor markers could enhance the sensitivity and specificity of the diagnosis and have a role as a basis for the personalized decision in lung cancer.

ctDNA, Lung Tumors, AUC, CEA, NSE

1. Alexander, E. M., Miller, H. A., Egger, M. E., Smith, M. L., Yaddanapudi, K., & Linder, M. W. (2024). The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden. The Journal of molecular diagnostics : JMD, 26(11), 952–961. https://doi.org/10.1016/j.jmoldx.2024.07.001
2. Bronkhorst, A. J., & Holdenrieder, S. (2023). The changing face of circulating tumor DNA (ctDNA) profiling: Factors that shape the landscape of methodologies, technologies, and commercialization. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V, 35(4), 201–235. https://doi.org/10.1515/medgen-2023-2065 
3. Dhillon, P., Du, S., & Cheng, H. (2025). Circulating Tumor DNA as a prognostic and predictive biomarker in lung cancer. Cancers, 17(20), 3327. https://doi.org/10.3390/cancers17203327 
4. Englisz, A., Smycz-Kubańska, M., Królewska-Daszczyńska, P., Błaut, M., Duszyc, A., & Mielczarek-Palacz, A. (2025). The Application of Circulating Tumour DNA (ctDNA) in the Diagnosis, Prognosis, and Treatment Monitoring of Gynaecological and Breast Cancers (Review). Diagnostics, 15(10), 1289. https://doi.org/10.3390/diagnostics15101289
5. Grunnet, M., & Sorensen, J. B. (2012). Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung cancer (Amsterdam, Netherlands), 76(2), 138–143. https://doi.org/10.1016/j.lungcan.2011.11.012
6. Lam, W. K. J., Bai, J., Ma, M. L., Cheung, Y. T. T., & Jiang, P. (2024). Circulating tumour DNA analysis for early detection of lung cancer: a systematic review. Annals of translational medicine, 12(4), 64. https://doi.org/10.21037/atm-23-1572 
7. Li, J. J., Lv, Y., & Ji, H. (2022). Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis. PeerJ, 10, e14303. https://doi.org/10.7717/peerj.14303
8. Li, S., Yuan, T., Yuan, J., Zhu, B., & Chen, D. (2024). Opportunities and challenges of using circulating tumor DNA to predict lung cancer immunotherapy efficacy. Journal of cancer research and clinical oncology, 150(11), 501. https://doi.org/10.1007/s00432-024-06030-8
9. Osumi, H., Shinozaki, E., Ooki, A., Shimozaki, K., Kamiimabeppu, D., Nakayama, I., Wakatsuki, T., Ogura, M., Takahari, D., Chin, K., & Yamaguchi, K. (2021). Correlation between circulating tumor DNA and carcinoembryonic antigen levels in patients with metastatic colorectal cancer. Cancer medicine, 10(24), 8820–8828. https://doi.org/10.1002/cam4.4384 
10. Sassorossi, C., Evangelista, J., Stefani, A., Chiappetta, M., Martino, A., Campanella, A., De Paolis, E., Nachira, D., Del Re, M., Guerrera, F., Boldrini, L., Urbani, A., Margaritora, S., Minucci, A., Bria, E., & Lococo, F. (2025). Genomics in Lung Cancer: A Scoping Review of the Role of ctDNA in Non-Advanced Non-Small-Cell Lung Cancer in the Prediction of Prognosis After Multimodality Therapeutic Approaches. Genes, 16(8), 962. https://doi.org/10.3390/genes16080962
11. Wan, J. C. M., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017). Liquid biopsies come of age: Towards implementation of circulating tumour DNA. Nature Reviews Cancer, 17(4), 223–238. https://doi.org/10.1038/nrc.2017.7
12. Wen, X., Pu, H., Liu, Q., Guo, Z., & Luo, D. (2022). Circulating Tumor DNA-A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques. Cancers, 14(24), 6025. https://doi.org/10.3390/cancers14246025
13. Yin, J. X., Hu, W. W., Gu, H., & Fang, J. M. (2021). Combined assay of Circulating Tumor DNA and Protein Biomarkers for early noninvasive detection and prognosis of Non-Small Cell Lung Cancer. Journal of Cancer, 12(4), 1258–1269. https://doi.org/10.7150/jca.49647
14. Yoon, J. K., Park, J. Y., Kim, Y. W., Oh, H. J., & Kim, Y. C. (2025). Advances and challenges in circulating tumor DNA-based early detection of lung cancer. Translational cancer research, 14(10), 7428–7437. https://doi.org/10.21037/tcr-2025-1332
15. Zaman, F. Y., Subramaniam, A., Afroz, A., Samoon, Z., Gough, D., Arulananda, S., & Alamgeer, M. (2023). Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis. Cancers, 15(9), 2425. https://doi.org/10.3390/cancers15092425 Alexander, E. M., Miller, H. A., Egger, M. E., Smith, M. L., Yaddanapudi, K., & Linder, M. W. (2024). The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden. The Journal of molecular diagnostics : JMD, 26(11), 952–961. https://doi.org/10.1016/j.jmoldx.2024.07.001
16. Bronkhorst, A. J., & Holdenrieder, S. (2023). The changing face of circulating tumor DNA (ctDNA) profiling: Factors that shape the landscape of methodologies, technologies, and commercialization. Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V, 35(4), 201–235. https://doi.org/10.1515/medgen-2023-2065 
17. Dhillon, P., Du, S., & Cheng, H. (2025). Circulating Tumor DNA as a prognostic and predictive biomarker in lung cancer. Cancers, 17(20), 3327. https://doi.org/10.3390/cancers17203327 
18. Englisz, A., Smycz-Kubańska, M., Królewska-Daszczyńska, P., Błaut, M., Duszyc, A., & Mielczarek-Palacz, A. (2025). The Application of Circulating Tumour DNA (ctDNA) in the Diagnosis, Prognosis, and Treatment Monitoring of Gynaecological and Breast Cancers (Review). Diagnostics, 15(10), 1289. https://doi.org/10.3390/diagnostics15101289
19. Grunnet, M., & Sorensen, J. B. (2012). Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung cancer (Amsterdam, Netherlands), 76(2), 138–143. https://doi.org/10.1016/j.lungcan.2011.11.012
20. Lam, W. K. J., Bai, J., Ma, M. L., Cheung, Y. T. T., & Jiang, P. (2024). Circulating tumour DNA analysis for early detection of lung cancer: a systematic review. Annals of translational medicine, 12(4), 64. https://doi.org/10.21037/atm-23-1572 
21. Li, J. J., Lv, Y., & Ji, H. (2022). Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis. PeerJ, 10, e14303. https://doi.org/10.7717/peerj.14303
22. Li, S., Yuan, T., Yuan, J., Zhu, B., & Chen, D. (2024). Opportunities and challenges of using circulating tumor DNA to predict lung cancer immunotherapy efficacy. Journal of cancer research and clinical oncology, 150(11), 501. https://doi.org/10.1007/s00432-024-06030-8
23. Osumi, H., Shinozaki, E., Ooki, A., Shimozaki, K., Kamiimabeppu, D., Nakayama, I., Wakatsuki, T., Ogura, M., Takahari, D., Chin, K., & Yamaguchi, K. (2021). Correlation between circulating tumor DNA and carcinoembryonic antigen levels in patients with metastatic colorectal cancer. Cancer medicine, 10(24), 8820–8828. https://doi.org/10.1002/cam4.4384 
24. Sassorossi, C., Evangelista, J., Stefani, A., Chiappetta, M., Martino, A., Campanella, A., De Paolis, E., Nachira, D., Del Re, M., Guerrera, F., Boldrini, L., Urbani, A., Margaritora, S., Minucci, A., Bria, E., & Lococo, F. (2025). Genomics in Lung Cancer: A Scoping Review of the Role of ctDNA in Non-Advanced Non-Small-Cell Lung Cancer in the Prediction of Prognosis After Multimodality Therapeutic Approaches. Genes, 16(8), 962. https://doi.org/10.3390/genes16080962
25. Wan, J. C. M., Massie, C., Garcia-Corbacho, J., Mouliere, F., Brenton, J. D., Caldas, C., Pacey, S., Baird, R., & Rosenfeld, N. (2017). Liquid biopsies come of age: Towards implementation of circulating tumour DNA. Nature Reviews Cancer, 17(4), 223–238. https://doi.org/10.1038/nrc.2017.7
26. Wen, X., Pu, H., Liu, Q., Guo, Z., & Luo, D. (2022). Circulating Tumor DNA-A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques. Cancers, 14(24), 6025. https://doi.org/10.3390/cancers14246025
27. Yin, J. X., Hu, W. W., Gu, H., & Fang, J. M. (2021). Combined assay of Circulating Tumor DNA and Protein Biomarkers for early noninvasive detection and prognosis of Non-Small Cell Lung Cancer. Journal of Cancer, 12(4), 1258–1269. https://doi.org/10.7150/jca.49647
28. Yoon, J. K., Park, J. Y., Kim, Y. W., Oh, H. J., & Kim, Y. C. (2025). Advances and challenges in circulating tumor DNA-based early detection of lung cancer. Translational cancer research, 14(10), 7428–7437. https://doi.org/10.21037/tcr-2025-1332
29. Zaman, F. Y., Subramaniam, A., Afroz, A., Samoon, Z., Gough, D., Arulananda, S., & Alamgeer, M. (2023). Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis. Cancers, 15(9), 2425. https://doi.org/10.3390/cancers15092425