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Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas

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Abstract

Purpose

Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated.

Methods

In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored.

Results

Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein–protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected.

Conclusion

Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

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Data availability

The data files can be downloaded from https://github.com/HuaChunY/GH-PA. The datasets are available from the corresponding author upon reasonable request.

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Acknowledgments

We want to thank and acknowledge all participants of the study.

Funding

This work was funded by the National Natural Science Foundation of China (81801369), Natural Science Foundation of Chongqing (No.cstc2019jcyj-msxmX0475), Nursery Project of Army Medical University (No.2019R054), and Clinical Research Project of Army Military Medical University (2018XLC3049).

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The collection procedure of patient tissue samples in this study was approved by laboratory animal welfare and ethics committee of Xinqiao Hospital (the ethical review number: 2018-049-012). All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Yin, H., Zheng, X., Tang, X. et al. Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas. J Endocrinol Invest 44, 1947–1959 (2021). https://doi.org/10.1007/s40618-021-01510-x

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