Avoiding Absolute Quantification Trap: A Novel Predictive Signature of Clinical Benefit to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer

Immunotherapy has been focused on by many oncologists and researchers. While, due to technical biases of absolute quantification, few traditional biomarkers for anti-PD-1 immunotherapy have been applied in regular clinical practice of non-small cell lung cancer (NSCLC). Therefore, there is an urgent and unmet need for a feasible tool-immune to data source bias-for identifying patients who might benefit from ICIs in clinical practice. Using the strategy based on the relative ranking of gene expression levels, we herein proposed the novel BRGP index (BRGPI): four BRGPs significantly related with progression-free survival of NSCLC patients treated with anti-PD-1 immunotherapy in the multicohort analysis. Moreover, stratification and multivariate Cox regression analyses demonstrated that BRGPI was an independent prognostic factor. Notably, compared to PD-L1, BRGPI exerted the best predictive ability. Further analysis showed that the patients in the BRGPI-low and PD-L1-high subgroup derived more clinical benefits from anti-PD-1 immunotherapy. In conclusion, the prospect of applying the BRGPI to real clinical practice is promising owing to its powerful and reliable predictive value.

Automated summary

Immunotherapy has drawn significant attention in oncology, but traditional biomarkers for anti-PD-1 therapy may not be suitable for NSCLC clinical practice due to technical biases. The novel BRGPI, a gene expression-based index, showed strong potential as a predictive tool for identifying NSCLC patients who may benefit from anti-PD-1 immunotherapy, outperforming PD-L1 as a prognostic factor. Patients with low BRGPI and high PD-L1 levels were found to derive more clinical benefits from anti-PD-1 therapy.