Advancing diagnostics, site specificity, and comorbidity insights in lung cancer through technological advances: Infrared Molecular Fingerprinting

Background: Infrared fingerprinting of cell-free blood for pan-molecular profiling has shown potential as a minimally invasive medical testing strategy for primary lung cancer in vitro diagnostics. However, lung cancer-specific signals in venous blood may be confounded by coexisting physiological abnormalities. Within-person stability of infrared molecular fingerprints has been demonstrated in longitudinal settings, yet not rigorously evaluated in a lung cancer screening context, where comorbidities may constrain the detection of disease-relevant molecular patterns. Methods: We combined Fourier-transform infrared (FTIR) spectroscopy with machine-learning-based multivariate analyses to capture complex feature dependencies. Molecular profiling of venous blood plasma across multiple clinical studies was performed to assess both, the potential and the limitations of the approach. Specifically, we systematically evaluated which coexisting health conditions could impair its diagnostic capacity. Results: We found that metabolic dysregulation did not significantly limit lung cancer detection, an important finding given the high prevalence of type-2 diabetes. Because kidney dysfunction frequently co-occurs with lung cancer, we also assessed its impact and found evidence that chronic kidney disease, along with COPD, reduced lung cancer detection performance through infrared profiling. These results highlight the need to account for specific comorbidities in order to optimize diagnostic accuracy. Conclusions: Robust diagnostic and prognostic tools to guide treatment in lung cancer patients are of urgent clinical relevance. While infrared molecular fingerprinting of cell-free blood (“liquid biopsy”) presents a promising new optical, label-free in vitro diagnostic strategy, its opportunities and limitations in the context of lung cancer and common comorbidities must be thoroughly understood to enable successful clinical implementation. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany