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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1511810
This article is part of the Research Topic Renewed Insight into Cancer Mechanism and Therapy View all articles

The Role of ATP6V0D2 in Breast Cancer: Associations with prognosis, immune characteristics, and TNBC progression

Provisionally accepted
Jingyu Zhang Jingyu Zhang 1Lixian Yang Lixian Yang 2*Bin Xu Bin Xu 1*Haibo Ji Haibo Ji 1*Shuo Liu Shuo Liu 1*Xiaohan Wang Xiaohan Wang 1*Xiaolong Li Xiaolong Li 3*Quanle Wang Quanle Wang 3*Zhenchuan Song Zhenchuan Song 1,4*
  • 1 Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 2 Department of Breast Surgery, Xingtai People's Hospital, Xingtai, China
  • 3 Department of Breast Surgery, Fourth Hospital of Shijiazhuang, Shijiazhuang, China
  • 4 Key Laboratory for Breast Cancer Molecular Medicine of Hebei Province, Shijiazhuang, China

The final, formatted version of the article will be published soon.

    Objective: Researches have identified ATPase H+ transporting V0 subunit d2 (ATP6V0D2) as a significant factor in various cancers. However, its prognostic value in breast cancer (BRCA) and its biological role in BRCA cells remain unclear.In this research, we examined the varying expression levels of ATP6V0D2 in both BRCA and normal breast tissue by utilizing information derived from databases including the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), along with clinical samples. Survival studies were carried out to investigate the link between ATP6V0D2 levels and prognosis in BRCA patients. A series of enrichment analyses identified possible pathways associated with the differentially expressed genes in BRCA. The relationships among ATP6V0D2 expression, immune characteristics, and gene mutation were evaluated using Spearman's test. Finally, the expression of ATP6V0D2 was identified by quantitative real-time polymerase chain reaction (RT-qPCR) alongside western blot analysis.Additionally, Cell Counting kit-8 (CCK-8), Colony formation, Transwell, Scratch healing, and Mouse xenograft tumor assays were conducted to assessed the impact of ATP6V0D2 knockdown on the biological functions in TNBC.Results: ATP6V0D2 exhibited high expression in a range of cancers and correlated with unfavorable prognosis in BRCA. Functional enrichment analyses revealed enrichment of extracellular matrix-receptor interaction, focal adhesion, and the signaling pathway of tumor growth factor-beta in the high ATP6V0D2 expression group. Additionally, ATP6V0D2 was closely associated with immune checkpoints. Its expression positively associated with the infiltration levels of macrophage and neutrophil, but inversely with CD8 + T and plasmacytoid dendritic cells. Mutation analysis revealed that PIK3CA, linked to decreased OS, exhibited a higher mutation 2 rate in the ATP6V0D2 high expression group. Furthermore, ATP6V0D2 knockdown inhibited TNBC cells invasion, migration, and proliferation abilities.ATP6V0D2 acts as a promising indicator for both diagnosis and prediction of outcomes in breast cancer and could potentially be a novel therapeutic target for BRCA.

    Keywords: ATP6v0d2, Immune infiltration, breast cancer, prognosis, diagnosis

    Received: 15 Oct 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Zhang, Yang, Xu, Ji, Liu, Wang, Li, Wang and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lixian Yang, Department of Breast Surgery, Xingtai People's Hospital, Xingtai, China
    Bin Xu, Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    Haibo Ji, Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    Shuo Liu, Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    Xiaohan Wang, Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    Xiaolong Li, Department of Breast Surgery, Fourth Hospital of Shijiazhuang, Shijiazhuang, China
    Quanle Wang, Department of Breast Surgery, Fourth Hospital of Shijiazhuang, Shijiazhuang, China
    Zhenchuan Song, Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China

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