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Utilizing bulk and single-cell RNA sequencing to identify potential biomarkers linked to angiogenesis and integrated stress response in chondrosarcoma
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  • Published: 21 February 2026

Utilizing bulk and single-cell RNA sequencing to identify potential biomarkers linked to angiogenesis and integrated stress response in chondrosarcoma

  • Shihong Li1 na1,
  • Jian Zhao1 na1,
  • Qingqing Qin1 na1,
  • Hai Huang2,
  • Dong Liu3,
  • Yang Liu4,
  • Dongyu Peng1,
  • Huimin Yu5,
  • Haohan Jing1,6,
  • Yucheng Wu1,6,
  • Feng Li1,
  • Zuzhi Meng7,
  • Dongfa Liao1,5,
  • Wei Wang1,5 &
  • …
  • Cairu Wang1,5 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Cancer
  • Computational biology and bioinformatics
  • Molecular biology

Abstract

Chondrosarcoma (CS) is the second most common bone sarcoma with a cartilage matrix. Angiogenesis and integrated stress response (ISR) exert a vital influence on the development of CS. This research aimed to conduct a comprehensive analysis to pinpoint angiogenesis and ISR-related potential biomarkers in CS and to elucidate their potential molecular mechanisms. CS data were from GEO. Potential biomarkers were identified and confirmed using differential expression analysis, WGCNA, and expression assessment. Moreover, enrichment analysis was employed to examine relevant pathways. Molecular regulatory network, compound prediction, and molecular docking analyses further explored the key regulatory roles of potential biomarkers in CS. GSE184118 was used to determine key cells and perform pseudo-time and cell communication analyses. Finally, RT-qPCR was used to confirm potential biomarker expression levels. Overall, three potential biomarkers (HSPA8, LMNA and SERPINH1) were determined, and their expression trends were consistent across the GSE30835 and GSE22855 datasets. Potential biomarkers were significantly enriched in the pathways like “medicus variant mutation caused aberrant HTT to 26S proteasome mediated protein degradation” in CS. Moreover, 9 transcription factors (TFs) (like STAT1), 69 key microRNAs (miRNAs) (like hsa-miR-361-3p), and 78 long non-coding RNAs (lncRNAs) (like NEAT1) were found to have relationships with potential biomarkers, and potential biomarkers had stable binding affinity with adenosine diphosphate (ADP) and lonafarnib. Moreover, pseudo-time analysis demonstrated a notable correlation between potential biomarkers’ expression and differentiation status of key cells (stromal cells (excluding leucocytes)), and cell communication revealed the strong interactions between stromal cells and chondroid clusters 1. Importantly, RT-qPCR confirmed higher expression of HSPA8, LMNA and SERPINH1 in CS patients. The findings suggested that HSPA8, LMNA and SERPINH1 might offer novel insights for the development of targeted therapies for CS associated with angiogenesis and ISR.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all members of our laboratory for their work.

Funding

The research reported in this project was generously supported by the Projects of Science and Technology of Sichuan Province (No. 2019YFS0122), the Hospital Project of the General Hospital of Western Theater Command (2021-XZYG-B06), and the “Xing Huo” Youth Innovation Talent Development Program of Western Theater Command General Hospital (41437 N).

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Author notes

  1. Shihong Li, Jian Zhao and Qingqing Qin contributed equally to this study and are co-first authors.

Authors and Affiliations

  1. The General Hospital of Western Theater Command, Chengdu, China

    Shihong Li, Jian Zhao, Qingqing Qin, Dongyu Peng, Haohan Jing, Yucheng Wu, Feng Li, Dongfa Liao, Wei Wang & Cairu Wang

  2. The Second Affiliated Hospital of Air Force Medical University, Xi’an, China

    Hai Huang

  3. The First Affiliated Hospital of Air Force Medical University, Xi’an, China

    Dong Liu

  4. Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province, Cangzhou, China

    Yang Liu

  5. College of Medicine, Southwest Jiaotong University, Chengdu, China

    Huimin Yu, Dongfa Liao, Wei Wang & Cairu Wang

  6. Chengdu Medical University, Chengdu, China

    Haohan Jing & Yucheng Wu

  7. The 950th Hospital of PLA, Yecheng, China

    Zuzhi Meng

Authors
  1. Shihong Li
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Contributions

Shihong Li, Dongfa Liao, Wei Wang and Cairu Wang participated in the conception and design of the study. Shihong Li, Jian Zhao and Qingqing Qin performed the research. Hai Huang, Dong Liu, Yang Liu, Dongyu Peng, Huimin Yu, Haohan Jing, Yucheng Wu, Feng Li and Zuzhi Meng analyzed the data. Shihong Li drafted the article. Dongfa Liao, Wei Wang and Cairu Wang reviewed the article. All authors had read and approved the final manuscript.

Corresponding authors

Correspondence to Dongfa Liao, Wei Wang or Cairu Wang.

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Li, S., Zhao, J., Qin, Q. et al. Utilizing bulk and single-cell RNA sequencing to identify potential biomarkers linked to angiogenesis and integrated stress response in chondrosarcoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40800-3

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  • Received: 24 October 2025

  • Accepted: 16 February 2026

  • Published: 21 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-40800-3

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Keywords

  • Chondrosarcoma
  • Angiogenesis
  • Integrated stress response
  • Single-cell RNA sequencing
  • Potential biomarkers
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