Genomic Analysis of the Prognostic Effect of Tumor-associated Neutrophil-related Genes Across 15 Solid Cancer Types: an Immune Perspective

Background: Tumor-associated neutrophils (TANs) have been a research hotspot in recent years. However, the role and relevant mechanisms of TANs in the tumor microenvironment (TME) have not yet been elucidated.

Method: The ribonucleic acid (RNA) expression levels of fucosyltransferase 4 (FUT4) and elastase, neutrophil expressed (ELANE) in samples from The Cancer Genome Atlas (TCGA) (n=4,538) were analyzed. Receiver operating characteristic (ROC) curves were used to calculate the critical cutoff values, and different data were defined as high and low expression. The tumor microenvironment immune type (TMIT) was defined according to the activation state of TAN, and the samples were classified into three TMITs based on their cut-off values. Mutational datasets and overall survival were compared according to the TMITs.

Results: The prognostic significance of FUT4, ELANE, and myeloperoxidase (MPO) was different among the 15 cancers, and the prognostic significance of different TMITs varied across the different tumors. Compared with the other groups, TMIT 3 had a favorable prognostic effect, which was most prominent in lung adenocarcinoma (LUAD) [hazard ratio (HR) =0.292, 95% confidence interval (CI): 0.185-0.459, P<0.001].

Conclusions: Our study demonstrated that highly-activated TANs predicted a favorable prognosis in humans using genomic analyses for the first time. This provides a realistic basis for further exploring the role of TANs in the immune microenvironment and provides real world data for tumor immunotherapy.