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Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer

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Abstract

Purpose

HER2-positive breast cancer (BC) accounts for 20–30% of all BC subtypes and is linked to poor prognosis. Trastuzumab (Tz), a humanized anti-HER2 monoclonal antibody, is a first-line treatment for HER2-positive breast cancer which faces resistance challenges. This study aimed to identify the biomarkers driving trastuzumab resistance.

Methods

Differential expression analysis of genes and proteins between trastuzumab-sensitive (TS) and trastuzumab-resistant (TR) cells was conducted using RNA-seq and iTRAQ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to study their functions. The prognostic significance and protein levels of ARFIP2 and MSN were evaluated using online tools and immunohistochemistry. Sensitivity of MSN and ARFIP2 to other therapies was assessed using public pharmacogenomics databases and the R language.

Results

Five genes were up-regulated, and nine genes were down-regulated in TR cells at both transcriptional and protein levels. Low ARFIP2 and high MSN expression linked to poor BC prognosis. MSN increased and ARFIP2 decreased in TR patients, correlating with shorter OS. MSN negatively impacted fulvestrant and immunotherapy sensitivity, while ARFIP2 had a positive impact.

Conclusion

Our findings suggest that MSN and ARFIP2 could serve as promising biomarkers for predicting response to Tz, offering valuable insights for future research in the identification of diagnostic and therapeutic targets for BC patients with Tz resistance.

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Data availability

The datasets generated and analyzed during the study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81703557), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Research Project of Jiangsu Cancer Hospital (ZM202002) and by college student innovation and entrepreneurship project.

Author information

Author notes

  1. Xiao Shi, Yuan Sheng, and Haoran Fei are contributed equally to this paper.

Authors and Affiliations

  1. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Key Laboratory of Marine Biotechnology, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China

    Xiao Shi, Haoran Fei, Bangbang Wei, Zhenyu Zhang, Xinyu Xia & Xinxin Si

  2. Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China

    Changfei Mao

  3. Department of Pharmacy, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211116, China

    Yuan Sheng

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  1. Xiao Shi
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  3. Haoran Fei
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Contributions

Xinxin Si and Bangbang collected data and conducted the data summary and statistical analysis. Haoran and Zhenyu Zhang performed experiments. Xinyu Yang and Changfei Mao searched for references and helped to write and revise the paper. Xiao Shi conducted data analysis and interpretation and wrote the manuscript. Yuan Sheng assembled data and reviewed the manuscript. Xiao Shi and Yuan Sheng reviewed and revised the paper. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Changfei Mao or Xinxin Si.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Informed consent

This study was approved by the Ethical Committee of Jiangsu Cancer Hospital and informed consent was obtained from all subjects and/or their legal guardian(s). All the experiments were conducted in accordance to the Declaration of Helsinki.

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Shi, X., Sheng, Y., Fei, H. et al. Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07355-1

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