MicroRNAs aid the assessment of programmed death ligand 1 expression in patients with non-small cell lung cancer.

ABSTRACT

The qualification of patients with non-small cell lung cancer (NSCLC) for anti-programmed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) antibody therapy is based on an immunohistochemistry (IHC) assessment of PD-L1 expression. Immunological checkpoint inhibitors improve the overall survival of patients with expression of PD-L1; however certain PD-L1-negative patients may also benefit from immunotherapy. This indicates the requirement for novel predictive factors for the qualification of immunotherapy. It is also necessary to understand the mechanisms that effect the expression of PD-L1 in tumor cells. The expression of PD-L1 in 47 formalin-fixed, paraffin-embedded, NSCLC specimens was assessed using IHC and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of 8 microRNAs (miRNAs, miRs) complementary to PD-L1-mRNA was also evaluated using RT-qPCR. A positive correlation was revealed between the expression level of PD-L1-mRNA and 2 miRs, miR-141 (R=0.533; P=0.0029) and miR-1184 (R=0.463; P=0.049). There was also a positive correlation between the percentage of PD-L1-positive tumor cells and the expression levels of miR-141 (R=0.441; P=0.0024), miR-200b (R=0.372; P=0.011) and miR-429 (R=0.430; P=0.0028), and between the percentage of the tumor area with immune cell infiltration and the expression levels of miR-141 (R=0.333; P=0.03) and miR-200b (R=0.312; P=0.046). Additionally, the percentage of tumor cells expressing PD-L1 positively correlated with miR-141 expression (R=0.407; P=0.0055). Correlations between the expression of the investigated miRs (particularly miR-141) and PD-L1 indicated that miRs may regulate PD-L1 expression at a post-transcriptional level.