Impact of NDUFAF6 on breast cancer prognosis: linking mitochondrial regulation to immune response and PD-L1 expression

Baohong Jiang; Sixuan Wu; Lijun Zeng; Yuanbin Tang; Lunqi Luo; Lianjie Ouyang; Wenjie Feng; Yeru Tan; Yuehua Li

doi:10.1186/s12935-024-03244-1

Cancer Cell International (Mar 2024)

Impact of NDUFAF6 on breast cancer prognosis: linking mitochondrial regulation to immune response and PD-L1 expression

Baohong Jiang,
Sixuan Wu,
Lijun Zeng,
Yuanbin Tang,
Lunqi Luo,
Lianjie Ouyang,
Wenjie Feng,
Yeru Tan,
Yuehua Li

Affiliations

Baohong Jiang: Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China
Sixuan Wu: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Lijun Zeng: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Yuanbin Tang: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Lunqi Luo: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Lianjie Ouyang: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Wenjie Feng: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Yeru Tan: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China
Yuehua Li: Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China

DOI: https://doi.org/10.1186/s12935-024-03244-1
Journal volume & issue: Vol. 24, no. 1
pp. 1 – 21

Abstract

Read online

Abstract Background Breast cancer is a major global health concern, and there is a continuous search for novel biomarkers to predict its prognosis. The mitochondrial protein NDUFAF6, previously studied in liver cancer, is now being investigated for its role in breast cancer. This study aims to explore the expression and functional significance of NDUFAF6 in breast cancer using various databases and experimental models. Methods We analyzed breast cancer samples from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases, supplemented with immunohistochemistry (IHC) staining to assess NDUFAF6 expression. A breast cancer cell xenograft mouse model was used to evaluate tumor growth, apoptosis, and NDUFAF6 expression. Survival probabilities were estimated through Kaplan–Meier plots and Cox regression analysis. A Protein–Protein Interaction (PPI) network was constructed, and differentially expressed genes related to NDUFAF6 were analyzed using GO, KEGG, and GSEA. The relationship between NDUFAF6 expression, immune checkpoints, and immune infiltration was also evaluated. Results NDUFAF6 was found to be overexpressed in breast cancer patients and in the xenograft mouse model. Its expression correlated with worse clinical features and prognosis. NDUFAF6 expression was an independent predictor of breast cancer outcomes in both univariate and multivariate analyses. Functionally, NDUFAF6 is implicated in several immune-related pathways. Crucially, NDUFAF6 expression correlated with various immune infiltrating cells and checkpoints, particularly promoting PD-L1 expression by inhibiting the NRF2 signaling pathway. Conclusion The study establishes NDUFAF6 as a potential prognostic biomarker in breast cancer. Its mechanism of action, involving the inhibition of NRF2 to upregulate PD-L1, highlights its significance in the disease's progression and potential as a target for immunotherapy.

Published in Cancer Cell International

ISSN: 1475-2867 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Science: Biology (General): Cytology
Website: https://cancerci.biomedcentral.com

About the journal

Abstract

Keywords