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Quantitative proteomics revealed the molecular characteristics of distinct types of granulated somatotroph adenomas

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Abstract

Purpose

Somatotroph adenomas are obviously heterogeneous in clinical characteristics, imaging performance, pathological diagnosis and therapeutic effect. The heterogeneity of the tumors, especially for SG and DG type adenomas, have attracted great interest in identifying the specific pathological markers and therapeutic targets of them. However, previous analyses of the molecular characteristics of the subtypes of somatotroph adenomas were performed at genomic and transcriptome level. The proteomic differences between the two subtypes of somatotroph adenomas are still unknown.

Methods

Tumor samples were surgically removed from 10 sporadic pituitary somatotroph adenoma patients and grouped according to the pathological type. Tandem mass tag (TMT)-based quantitative proteomic analysis was employed to analyze the proteomic differences between SG and DG tumors.

Results

In total, 228 differentially expressed proteins were identified between SG adenomas and DG adenomas. They were enriched mainly in extracellular matrix (ECM)-receptor interaction, leukocyte transendothelial migration, arrhythmogenic right ventricular cardiomyopathy and DNA replication pathways. Protein-protein interaction (PPI) network analysis indicated that Cadherin-1 and Catenin beta-1 were the most important key proteins in the differences between SG and DG adenomas. Immunohistochemistry (IHC) confirmed the expression levels of the key proteins.

Conclusions

This study provides large-scale proteome molecular characteristics of distinct granulation subtypes of somatotroph adenomas. Compared with DG adenomas, The differential protein of SG adenomas mostly enrich in invasive and proliferative functions and pathways at the proteomic level. Cadherin-1 and Catenin beta-1 play key roles in the different biological characteristics of the two tumor subtypes.

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Acknowledgements

We thank and acknowledge all of the participants in the study.

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Foundation of Science and Technology Commission of Shanghai Municipality (19ZR1409800).

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  1. These authors contributed equally: Yifan Tang, Tao Xie, Silin Wu

Authors and Affiliations

  1. Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China

    Yifan Tang, Tao Xie, Silin Wu, Tengfei Liu, Chen Li, Shuang Liu, Zhiyong Shao & Xiaobiao Zhang

  2. Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

    Qiaoqiao Yang

  3. State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China

    Zhiyong Shao

  4. Digital Medical Research Center, Fudan University, Shanghai, China

    Xiaobiao Zhang

  5. Shanghai Key Laboratory of Medical Image Computing and Computer-Assisted Intervention, Shanghai, China

    Xiaobiao Zhang

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Tang, Y., Xie, T., Wu, S. et al. Quantitative proteomics revealed the molecular characteristics of distinct types of granulated somatotroph adenomas. Endocrine 74, 375–386 (2021). https://doi.org/10.1007/s12020-021-02767-1

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