Plasma complement C7 as a target in non-small cell lung cancer patients to implement 3P medicine strategies.

Background: Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) significantly affect outcomes in non-small cell lung cancer (NSCLC) patients. However, differences in reactions toward PD-1/PD-L1 ICI among patients impose inefficient treatment. Therefore, developing a reliable biomarker to predict PD-1/PD-L1 ICI reaction is highly necessary for predictive, preventive, and personalized (3P) medicine.

Materials and methods: We recruited 63 patients from the National Cancer Center (NCC) and classified them into the training and validation sets. Next, 99 patients were recruited for inclusion into the external validation set at the Samsung Medical Center (SMC). Proteomic analysis enabled us to identify plasma C7 levels, which were significantly different among groups classified by their overall response to the RECIST V 1.1-based assessment. Analytical performance was evaluated to predict the PD-1/PD-L1 ICI response for each type of immunotherapy, and NSCLC histology was evaluated by determining the C7 levels via ELISA.

Results: Plasma C7 levels were significantly different between patients with and without clinical benefits (PFS ≥ 6 months). Among the groups sorted by histology and PD-1/PD-L1 immunotherapy type, only the predicted accuracy for pembrolizumab-treated patients from both NCC and SMC was greater than 73%. In patients treated with pembrolizumab, C7 levels were superior to those of the companion diagnostics 22C3 (70.3%) and SP263 (62.1%). Moreover, for pembrolizumab-treated patients for whom the PD-L1 tumor proportion score (TPS) was < 50%, the predictive accuracy of C7 was nearly 20% higher than that of 22C3 and SP263.

Conclusion: Evaluation of plasma C7 levels shows an accurate prediction of NSCLC patient reactions on pembrolizumab. It demonstrates plasma C7 is an alternative and supportive biomarker to overcome the predictive limitation of previous 22C3 and SP263. Thus, it is clear that clinical use of plasma C7 allows predictive diagnosis on lung cancer patients who have not been successfully treated with current CDx and targeted prevention on metastatic diseases in secondary care caused by a misdiagnosis of current CDx. Reduction of patients' financial burden and increased efficacy of cancer treatment would also enable prediction, prevention, and personalization of medical service on NSCLC patients. In other words, plasma C7 provides efficient medical service and an optimized medical economy followed which finally promotes the prosperity of 3P medicine.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-021-00266-x.