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Breast Cancer Research and Treatment

15.05.2024 | Research

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

verfasst von: Xiao Shi, Yuan Sheng, Haoran Fei, Bangbang Wei, Zhenyu Zhang, Xinyu Xia, Changfei Mao, Xinxin Si

Erschienen in: Breast Cancer Research and Treatment

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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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Metadaten
Titel
Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer
verfasst von
Xiao Shi
Yuan Sheng
Haoran Fei
Bangbang Wei
Zhenyu Zhang
Xinyu Xia
Changfei Mao
Xinxin Si
Publikationsdatum
15.05.2024
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-024-07355-1

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