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Data-independent acquisition (DIA) mass spectrometry reveals related proteins involved in the occurrence of early intestinal-type gastric cancer

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Abstract

Identifying proteins associated with the onset of early intestinal-type gastric cancer (EIGC) can yield valuable insights into the pathogenesis of this specific subtype of gastric cancer. Data-independent acquisition mass spectroscopy (DIA-MS) was utilized to identify the differential protein between 10 cases of EIGC and atrophic gastritis with intestinal metaplasia (NGC). The expressions of IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were verified by immunohistochemistry (IHC) in 20 EIGC samples, 17 gastric low-grade intraepithelial neoplasia (LGIN) samples, and 21 healthy controls. The prognostic values of the five genes were validated in the transcriptome data by survival analysis. A total of 4,028 proteins were identified using DIA-MS and a total of 177 differential proteins were screened with log2(fold change) > 1.5. Among them, 113 proteins were significantly up-regulated, and 64 proteins were significantly down-regulated in EIGC tissues. IHC results showed that proteins IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were highly expressed in the cytoplasm of EIGC and LGIN, which was consistent with the results of DIA-MS. Among them, p62/SQSTM1 may undergo nuclear-cytoplasmic transfer. The five protein-coding genes were associated with intestinal-type gastric cancer survival and exhibited differential expression across various disease stages. The study successfully identified differentially expressed proteins between EIGC and NGC, providing potential biomarkers and valuable insights into the mechanism underlying intestinal-type gastric cancer.

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Data availability

The datasets analyzed in the study are available in public repositories at NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/).

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Acknowledgements

We are grateful for the technical support from Shanghai Applied Protein Technology Co. Ltd. This study was funded by the Zhejiang Provincial Natural Science Foundation of China (Nos. LGF19H030006 and LQ20H030001), Ningbo Science and Technology Project (No. 2019C50100), and Ningbo Clinical Medicine Research Center Project (No. 2019A21003).

Funding

This article was funded by Zhejiang Provincial Natural Science Foundation of China, LGF19H030006, Hua Ye, LQ20H030001, Hua Ye, Ningbo Science and Technology Project, 2019C50100, Hua Ye,Ningbo Clinical Medicine Research Center Project, 2019A21003, Hong Li.

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Authors and Affiliations

  1. The Affiliated Lihuili Hospital, Ningbo University, Ningbo, 315046, Zhejiang, People’s Republic of China

    Liangshun Zhang, Feng Xu, Hongna Lu, Xianwen Dong, Zhiqiang Gao, Qiaosu Zhao, Ting Weng, Hong Li & Hua Ye

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  1. Liangshun Zhang
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Contributions

Hua Ye and Hong Li: conceived and designed the experiments. Liangshun Zhang and Feng Xu: collected samples, performed the proteome analysis, and analysed the data. Hongna Lu and Xianwen Dong: data analysis and plotting figures. Zhiqiang Gao and Qiaosu Zhao: performed the WGCNA and transcriptome data analysis. Ting Weng: survival analysis. Hong Li: drafting the manuscript. Hua Ye: project administration and revised the manuscript. All the authors participated in the manuscript revision.

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Correspondence to Hong Li or Hua Ye.

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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.

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The experimental protocol was approved by the Ethics Committee of Ningbo Medical Center Lihuili Hospital (KY2019PJ055). Informed consent was obtained from all participating patients or their family members.

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Zhang, L., Xu, F., Lu, H. et al. Data-independent acquisition (DIA) mass spectrometry reveals related proteins involved in the occurrence of early intestinal-type gastric cancer. Med Oncol 41, 23 (2024). https://doi.org/10.1007/s12032-023-02241-0

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