A comprehensive pan-cancer analysis of gene amplification, tumor mutation burden, microsatellite instability, and PD-L1 expression in Chinese cancer patients.

BACKGROUND

Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need.

METHODS

This study retrospectively analyzed clinical information and genetic profiling results of 16,013 samples from Chinese patients with various cancer types in order to investigate the prevalence of (also known as PD-L1) amplification in various cancer types and its association with existing PD-1/PD-L1 biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression.

RESULTS

Amplification of was identified in 174 samples with an overall prevalence of 1.09% among all cancer types in the cohort. The prevalence of amplification in different cancer types and histological subtypes of lung cancer was varied, with cervical cancer having the highest prevalence. Distinct distributions of TMB, MSI, and PD-L1 expression between amplified and wild-type samples were observed in several cancer types as well as among different histological subtypes of lung cancer.

CONCLUSIONS

Although amplification was only observed in a small proportion of patients, it demonstrated an association with TMB, MSI, and PD-L1 expression in several common cancer types. The molecular features of in different cancer types are heterogeneous. The role of amplification as a novel biomarker of PD-1/PD-L1 inhibitors remains to be characterized in future prospective clinical studies.