Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.
Mirte Muller, Myron G Best, Vincent van der Noort, T Jeroen N Hiltermann, Anna-Larissa N Niemeijer, Edward Post, Nik Sol, Sjors G J G In 't Veld, Tineke Nogarede, Lisanne Visser, Robert D Schouten, Daan van den Broek, Karlijn Hummelink, Kim Monkhorst, Adrianus J de Langen, Ed Schuuring, Egbert F Smit, Harry J M Groen, Thomas Wurdinger, Michel M van den Heuvel
Author Information
Mirte Muller: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Myron G Best: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Boelelaan, Amsterdam, the Netherlands.
Vincent van der Noort: Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
T Jeroen N Hiltermann: Department of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Anna-Larissa N Niemeijer: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Boelelaan, Amsterdam, The Netherlands.
Edward Post: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Boelelaan, Amsterdam, the Netherlands.
Nik Sol: Cancer Center Amsterdam and Liquid Biopsy Center, Amsterdam, The Netherlands.
Sjors G J G In 't Veld: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Boelelaan, Amsterdam, the Netherlands.
Tineke Nogarede: Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Lisanne Visser: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Boelelaan, Amsterdam, the Netherlands.
Robert D Schouten: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Daan van den Broek: Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Karlijn Hummelink: Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Kim Monkhorst: Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Adrianus J de Langen: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ed Schuuring: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Egbert F Smit: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Boelelaan, Amsterdam, The Netherlands.
Harry J M Groen: Department of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Thomas Wurdinger: Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, Boelelaan, Amsterdam, the Netherlands.
Michel M van den Heuvel: Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
BACKGROUND: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content. OBJECTIVE: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses. METHODS: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm. RESULTS: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63-0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51-0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45-0.70, n = 107 samples)), employing a five-RNAs biomarker panel. CONCLUSIONS: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application.
