# Acetylated Pyrimidine Metabolism Genes as Prognostic Markers and Their Influence on Immune Profiles in Lung Adenocarcinoma

## TL;DR

This study identifies acetylated pyrimidine metabolism genes as potential prognostic markers and explores their impact on immune profiles in lung adenocarcinoma.

## Contribution

The study introduces acetylated pyrimidine metabolism genes as novel prognostic indicators linked to immune infiltration in lung adenocarcinoma.

## Key findings

- Three genes (TK1, RRM2B, NME4) were identified as prognostic markers using CoxBoost and random forest survival analysis.
- Low-risk patients based on gene activity and acetylation showed better survival and higher antitumor immune cell infiltration.
- TK1 promotes tumor aggressiveness, confirmed through RNA interference and functional assays.

## Abstract

Lung adenocarcinoma is a very aggressive cancer with poor clinical results. New molecular indicators are desperately needed to improve treatment decision‐making. This study looks at the relationship between the immunological microenvironment and genes linked to pyrimidine metabolism, particularly those that undergo acetylation, and the prognostic significance of these genes. Using publicly accessible genomic and clinical data, we used Gene Set Variation Analysis (GSVA) to identify acetylated pyrimidine pathway components that are highly correlated with survival outcomes. Three potential genes—TK1, RRM2B, and NME4—were identified for their prognostic relevance by using sophisticated predictive modeling approaches including CoxBoost and a random forest survival analysis. Using CIBERSORT deconvolution and single‐sample gene set enrichment, immunological landscape disparities were identified, and it was discovered that varied gene expression‐acetylation patterns were linked to varying immune cell infiltration. Gene activity and acetylation status‐based low‐risk patients showed positive survival patterns and higher levels of antitumor immune populations, indicating possible receptivity to immune‐based treatments. Functional validation experiments targeting TK1, including RNA interference followed by proliferation (CCK‐8, EdU), migration (Transwell), and wound healing assays, substantiated its role in promoting tumor aggressiveness. Collectively, our findings suggest that integrating metabolic gene signatures with immunological context offers a promising framework for precision oncology in lung adenocarcinoma.