Integrative Multi-Omics Analysis and Experiments Validation Identify COX5B as a Novel Therapeutic Target for Lung Adenocarcinoma
Lv Ling1,#, Minying Lu2,#, Ling Ye3, Yuanhang Chen2, Sheng Lin2, Jun Yang2, Yu Rong2,*, Guixiong Wu4,*
1 Department of Thoracic Surgery, Panyu Hospital of Traditional Chinese Medicine, Guangzhou, 511400, China
2 Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510095, China
3 Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
4 Department of Respiratory Medicine, The People’s Hospital of Wuzhou, Wuzhou, 543000, China
* Corresponding Author: Yu Rong. Email: 
; Guixiong Wu. Email: 
# These authors contributed equally to this work
(This article belongs to the Special Issue: Novel Targets and Biomarkers in Solid Tumors)
Oncology Research https://doi.org/10.32604/or.2025.069889
Received 02 July 2025; Accepted 26 September 2025; Published online 30 October 2025
Abstract
Background: A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies, making the search for new treatment strategies extremely urgent. In this study, we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma (LUAD).
Methods: We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B (COX5B) in LUAD. Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD. To further elucidate the role of COX5B in LUAD, we utilized multiple experimental approaches, including quantitative reverse transcription PCR assays, western blot, immunohistochemistry, electron microscopy, flow cytometry, and EdU proliferation assays.
Results: We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients. Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate (ATP) synthesis through the oxidative phosphorylation pathway. There was a negative correlation between COX5B expression and immune infiltration in LUAD. Furthermore, we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines. Specifically, immunohistochemistry (IHC) assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues (
p = 0.0044). Additionally, COX5B knockdown disrupted the redox homeostasis, ultimately suppressed the proliferation of LUAD cells. Subsequent investigations demonstrated that berberine effectively targeted COX5B, diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.
Conclusions: This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD, elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth, thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
Graphical Abstract
Keywords
Lung adenocarcinoma (LUAD); cytochrome C oxidase 5B (COX5B); prognosis; proliferation; berberine
Open Access
Login
Register
Submit a Paper
Propose a Special lssue
Download PDF
Supplementary Material File
Downloads
Citation Tools
