Dados do Trabalho

Título

PD-L1 expression is associated with reactive oxygen response, metabolic and androgen receptor genes in melanoma

Introdução

Immune checkpoints, such as Programmed Death Ligand-1 (PD-L1), have been highlighted by their importance as prognostic biomarkers and/or used as a predictor of immune checkpoint therapy response. The expression of PD-L1 may be induced by extrinsic pathways, like inflammatory cytokines, or intrinsic pathways, including oncogenic signaling. The comprehension of intrinsic pathways and genes associated with PD-L1 expression could contribute to the understanding of tumor evasion mechanisms.

Objetivo

To evaluate genes associated with PD-L1 expression in advanced melanoma.

Métodos

Fifty-two patients with melanoma with a minimum of 60% of tumor cells in formalin-fixed, paraffin-embedded (FFPE) tissue were included. PD-L1 expression was assessed by immunohistochemistry using the Benchmark® ULTRA platform and the anti-PD-L1 antibody (Cell Signaling Technology®, clone E1L3N, dilution 1:200). The tumor proportion score was evaluated in a minimum of 100 viable tumor cells. Gene count (GC) was evaluated in RNA samples submitted to the Metabolic Pathways Panel using the nCounter NanoString (NanoString Technologies). Results were normalized by housekeeping genes in nSolver Analysis Sofware v. 4.0. Statistical analyses were performed in SPSS 23.0 software using Spearman Correlation and Multiple Linear Regression tests. The study was approved by the Institutional Ethics Research Committee (nº 1772/2019).

Resultados

PD-L1 expression was detected in 6% of cases, with expression varying between 10 to 15%. In univariate analysis, 34 genes were correlated with PD-L1 expression. Multiple Linear Regression indicated three genes with a higher prediction of PD-L1 expression: HPD, SOD3, and AR. The model was statistically significant [F (3, 48)=4.511; p=0.007; R²=0.469].

Conclusões

This screening highlights that reactive oxygen response (SOD3), metabolic pathway (HPD), and androgen receptor (AR) genes could induce PD-L1 expression and may be associated with tumor evasion.

Palavras-chave

Melanoma; PD-L1; Tumor biomarkers

Financiador do resumo

This research was funded by the São Paulo Research Foundation (FAPESP, #2019/07111-9) and the Researchers Assistance and Incentive Program (PAIP - Barretos Cancer Hospital).