Publicação
Immunodiagnostic plasma amino acid residue biomarkers detect cancer early and predict treatment response
| Resumo: | 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. |
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| Autores principais: | Tang, Cong |
| Outros Autores: | Corredeira, Patrícia; Casimiro, Sandra; Shi, Qi; Han, Qiwei; Sukdao, Wesley; Cavaco, Ana; Melo-Alvim, Cecília; Matos, Carolina Ochôa; Abreu, Catarina; Walsh, Steven; Nogueira-Costa, Gonçalo; Ribeiro, Leonor; Sousa, Rita; Barradas, Ana Lorena; Fonseca, João Eurico; Costa, Luís; Yates, Emma V; Bernardes, Gonçalo J L |
| Assunto: | Humans Biomarkers, Tumor/blood Female Amino Acids/blood Neoplasms/diagnosis Breast Neoplasms/blood Male Middle Aged Early Detection of Cancer/methods Adult Aged Treatment Outcome SDG 3 - Good Health and Well-being |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | 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. |
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