Immunodiagnostic plasma amino acid residue biomarkers detect cancer early and predict treatment response.
Journal:
Nature communications
Published Date:
Jul 14, 2025
Abstract
The immune response to tumour development is frequently targeted with therapeutics but remains largely unexplored in diagnostics, despite being stronger for early-stage tumours. We present an immunodiagnostic platform to detect this. We identify a panel of amino acid residue biomarkers providing a signature of cancer-specific immune activation associated with tumour development and distinct from autoimmune and infectious diseases, measurable optically in neat blood plasma, and validate within N = 170 participants. By measuring the total concentrations of cysteine, free cysteine, lysine, tryptophan, and tyrosine protein-incorporated biomarkers and analyzing the results with supervised machine learning, we identify 78% of cancers with 0% false positive rate (N = 97) with an AUROC of 0.95. The cancer, healthy, and autoimmune/infectious biomarker pattern are statistically significantly different (p < 0.0001). Smaller-scale changes in biomarker concentrations reveal inter-patient differences in immune activation that predict treatment response. Specific concentration ranges of these biomarkers predict response to Cyclin-dependent kinase inhibitors in advanced breast cancer patients (p < 0.05), identifying 98% of responders (N = 33). Here we provide an immunodiagnostic technology platform that, to our knowledge, has not been previously reported, and prove initial clinical application in a cohort of N = 170, including proof of concept in Multi Cancer Early Detection and personalized medicine.