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<p>Cisplatin is the primary chemotherapeutic agent for osteosarcoma. However, a significant proportion of patients develop resistance post-treatment, leading to disease recurrence and presenting profound clinical challenges. To understand the mechanisms underlying osteosarcoma recurrence and cisplatin resistance, particularly from the tumor microenvironment perspective, we consolidated numerous single-cell RNA sequencing datasets, offering an encompassing insight into the osteosarcoma microenvironment. When juxtaposing scRNA-seq with bulk RNA-seq data, we observed a strong correlation between high <i>DCUN1D5</i> expression in osteosarcoma and patient survival. This gene amplifies osteosarcoma’s anti-apoptotic, invasive, stem-cell-like traits and PI3K/AKT/GSK3β pathway phosphorylation and fosters cisplatin resistance. Subsequent research revealed that cisplatin-resistant osteosarcoma cells excrete <i>DCUN1D5</i>-rich exosomes, facilitating the maturation of osteoclast precursors. Excessive osteoclast activity is a pivotal contributor to osteosarcoma recurrence and resistance. Given these insights, <i>DCUN1D5</i> is a promising therapeutic target for osteosarcoma recurrence and drug resistance.</p><p></p>

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Single-cell analysis links DCUN1D5 to immune remodeling and cisplatin resistance in recurrent osteosarcoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月8日

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  • Xin Wu,
  • Woding Deng,
  • Qiangqiang Zhao,
  • Jianbin Xiong

摘要

Cisplatin is the primary chemotherapeutic agent for osteosarcoma. However, a significant proportion of patients develop resistance post-treatment, leading to disease recurrence and presenting profound clinical challenges. To understand the mechanisms underlying osteosarcoma recurrence and cisplatin resistance, particularly from the tumor microenvironment perspective, we consolidated numerous single-cell RNA sequencing datasets, offering an encompassing insight into the osteosarcoma microenvironment. When juxtaposing scRNA-seq with bulk RNA-seq data, we observed a strong correlation between high DCUN1D5 expression in osteosarcoma and patient survival. This gene amplifies osteosarcoma’s anti-apoptotic, invasive, stem-cell-like traits and PI3K/AKT/GSK3β pathway phosphorylation and fosters cisplatin resistance. Subsequent research revealed that cisplatin-resistant osteosarcoma cells excrete DCUN1D5-rich exosomes, facilitating the maturation of osteoclast precursors. Excessive osteoclast activity is a pivotal contributor to osteosarcoma recurrence and resistance. Given these insights, DCUN1D5 is a promising therapeutic target for osteosarcoma recurrence and drug resistance.