Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

Silvia Baldari; Annalisa Antonini; Giuliana Di Rocco; Gabriele Toietta

doi:10.1002/cai2.149

Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

Cancer Innov. 2024 Dec 5;4(1):e149. doi: 10.1002/cai2.149. eCollection 2025 Feb.

Authors

Silvia Baldari¹, Annalisa Antonini¹, Giuliana Di Rocco², Gabriele Toietta¹

Affiliations

¹ Tumor Immunology and Immunotherapy Unit IRCCS Regina Elena National Cancer Institute Rome Italy.
² Unit of Cellular Networks and Molecular Therapeutic Targets IRCCS Regina Elena National Cancer Institute Rome Italy.

Abstract

Background: The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.

Methods: We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD).

Results: Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial-mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD.

Conclusions: A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.

Keywords: acetaldehyde; alcohol; aldehyde dehydrogenase; ethanol metabolism; immunotherapy; lung adenocarcinoma; mitochondria; rs671 polymorphism (Glu504Lys) of aldehyde dehydrogenase 2.