ALDH2 as a potential stem cell-related biomarker in lung adenocarcinoma: Comprehensive multi-omics analysis

Thi-Oanh Tran; Thanh Hoa Vo; Luu Ho Thanh Lam; Nguyen Quoc Khanh Le

doi:10.1016/j.csbj.2023.02.045

ALDH2 as a potential stem cell-related biomarker in lung adenocarcinoma: Comprehensive multi-omics analysis

Comput Struct Biotechnol J. 2023 Feb 24:21:1921-1929. doi: 10.1016/j.csbj.2023.02.045. eCollection 2023.

Authors

Thi-Oanh Tran^{1

2}, Thanh Hoa Vo^{3

4}, Luu Ho Thanh Lam^{5

6}, Nguyen Quoc Khanh Le^{7

8

9}

Affiliations

¹ International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
² Hematology and Blood Transfusion Center, Bach Mai Hospital, No.78, Giai Phong street, Hanoi, Viet Nam.
³ Department of Science, School of Science and Computing, South East Technological University, Waterford X91 K0EK, Ireland.
⁴ Pharmaceutical and Molecular Biotechnology Research Center (PMBRC), South East Technological University, Waterford X91 K0EK, Ireland.
⁵ Department of Pediatrics, Pham Ngoc Thach University of Medicine, Ho Chi Minh city, Viet Nam.
⁶ Children's Hospital 1, Ho Chi Minh city, Viet Nam.
⁷ Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei 106, Taiwan.
⁸ Research Center for Artificial Intelligence in Medicine, Taipei Medical University, Taipei 106, Taiwan.
⁹ Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan.

Abstract

Lung adenocarcinoma (LUAD) is the most prevalent lung cancer and one of the leading causes of death. Previous research found a link between LUAD and Aldehyde Dehydrogenase 2 (ALDH2), a member of aldehyde dehydrogenase gene (ALDH) superfamily. In this study, we identified additional useful prognostic markers for early LUAD identification and targeting LUAD therapy by analyzing the expression level, epigenetic mechanism, and signaling activities of ALDH2 in LUAD patients. The obtained results demonstrated that ALDH2 gene and protein expression significantly downregulated in LUAD patient samples. Furthermore, The American Joint Committee on Cancer (AJCC) reported that diminished ALDH2 expression was closely linked to worse overall survival (OS) in different stages of LUAD. Considerably, ALDH2 showed aberrant DNA methylation status in LUAD cancer. ALDH2 was found to be downregulated in the proteomic expression profile of several cell biology signaling pathways, particularly stem cell-related pathways. Finally, the relationship of ALDH2 activity with stem cell-related factors and immune system were reported. In conclusion, the downregulation of ALDH2, abnormal DNA methylation, and the consequent deficit of stemness signaling pathways are relevant prognostic and therapeutic markers in LUAD.

Keywords: 4-HNE, 4-Hydroxynonenal; AJCC, American Joint Committee On Cancer; ALDH, Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 2; CGI, Cpg Island; CPTAC, Clinical Proteomic Tumor Analysis Consortium; CSCs, Cancer Stem Cells; Cancer stem cells; DNA methylation; Gene expression; IHC, Immunohistochemical; LCSCs, Liver Cancer Stem Cells; LUAD, Lung Adenocarcinoma; Lung adenocarcinoma; MAPK, Mitogen-Activated Protein Kinase; MDA, Malondialdehyde; NSCLC, Non-Small Cell Lung Cancer; OS, Overall Survival; Protein expression; ROS, Reactive Oxygen Species; SCLC, Small Cell Lung Cancer; Survival analysis; TCGA, The Cancer Genome Atlas; TMT, Tandem Mass Tags; TNM, Tumor-Node-Metastasis; UICC, International Union For Cancer Control; XRCC1, X-Ray Repair Cross-Complementing Protein 1.