Construction and validation of a lactylation-based gene signature for prognostic assessment and immune infiltration analysis in gastric adenocarcinoma.

Abstract

Background: Stomach adenocarcinoma (STAD) poses a major public health challenge across various populations, necessitating the construction of robust models for prognostic prediction and effective clinical therapies. Dysregulation of lactylation, a key regulatory mechanism in cell metabolism and gene expression, can either impede or promote tumor growth and metastasis.

Methods: This study got into the bottom of TCGA-STAD-sourced transcriptome data to profile lactylation-related genes and construct a gene signature through LASSO regression. A nomogram was further created to assess the prognostic performance of this model. Our investigation primarily concentrated on the expression of Dehydrogenase/reductase 7 (DHRS7) in STAD, with the verification of its correlations with clinical characteristics, immune cell infiltration, and cellular signaling pathways.

Results: DHRS7 expressed lower in STAD tissues, and that modulating DHRS7 levels could either promote or inhibit malignant behaviors associated with STAD. In the later stages of tumor progression, DHRS7 appeared to facilitate tumor growth through mechanisms such as immune evasion and activation of PI3K/AKT/mTOR signaling pathways, ultimately contributing to an unfavorable prognosis.

Conclusions: DHRS7 has the potential to shift from acting as a tumor suppressor to functioning as an oncogene in modified TMEs, despite its lower expression levels in STAD tissues relative to normal tissues. This transformation accounts for the association between high DHRS7 expression in the later stages of STAD and a negative prognosis.