Distinct Prognostic and Immunological Roles of ETS1 and ETS2: A Pan‐Cancer Analysis

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Abstract
Objective. ETS1 and ETS2, the main ETS family of transcription factors, have been found to act as downstream effectors of the RAS/MAPK pathway. This study explores the expression and prognostic values of ETS1 and ETS2 across cancers. We also aimed to explore the significance of ETS1 and ETS2 expression in normal immune cells with relation to tumorigenesis. Methods. The expression of ETS1 and ETS2 was examined in the HPA and GEPIA2 databases. The KM plotter was applied to examine prognostic value of ETS1 and ETS2. Correlation between ETS1/ETS2 and infiltrating immune cells and immune checkpoints was assessed using TIMER2.0. The mutation landscape of ETS1/ETS2 was explored using the cBioPortal. STRING and GEPIA2 were used to screen ETS1/ETS2 binding and correlated genes. Enrichr was applied to perform GO and KEGG enrichment analyses. Results. ETS1 showed enhanced expression in lymphoid tissue, while ETS2 showed low tissue specificity. ETS1 was increased in 12 and decreased in 6 cancers, while ETS2 was increased in 4 and decreased in 13 cancers. Both ETS1 and ETS2 were favorable prognostic markers in LIHC and KIRC, while they showed different prognostic roles in more cancers. ETS1 showed stronger correlation with several infiltrating immune cells and immune checkpoints compared with ETS2. Both ETS1 and ETS2 harbored low mutation ratio. ETS1 interacting and correlated genes were enriched in GO terms in response to cadmium ion and response to oxidative stress, while those of ETS2 were enriched in transcription regulation. Conclusion. ETS1 and ETS2 showed different patterns in expression, prognostic values, correlation with immune infiltrating, and immune checkpoints. ETS1 and ETS2 play distinct roles across cancer.

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