Identification of HSPD1 as a novel invasive biomarker associated with mitophagy in pituitary adenomas

Yu Zhang; Xin Ma; Congyu Liu; Zhixu Bie; Gemingtian Liu; Pinan Liu; Zhijun Yang

doi:10.1016/j.tranon.2024.101886

Identification of HSPD1 as a novel invasive biomarker associated with mitophagy in pituitary adenomas

Transl Oncol. 2024 Mar:41:101886. doi: 10.1016/j.tranon.2024.101886. Epub 2024 Jan 29.

Authors

Yu Zhang¹, Xin Ma¹, Congyu Liu², Zhixu Bie¹, Gemingtian Liu¹, Pinan Liu³, Zhijun Yang⁴

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.
² School of Life Science, Tsinghua University, Beijing, PR China.
³ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China; Department of Neural Reconstruction, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China. Electronic address: pinanliu@ccmu.edu.cn.
⁴ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China. Electronic address: zhijunyang@ccmu.edu.cn.

Abstract

Background: The crucial role of mitophagy in tumor progression has been recognized. Therefore, our study aimed to investigate the potential correlation between pituitary adenoma invasiveness and the mitophagy processes.

Methods: In this study, we used transcriptomics of postoperative tissue from 32 patients and quantitative proteomics of 19 patients to screen for mitophagy-related invasion genes in pituitary adenomas. The invasive predictive value of target genes was analyzed by Lasso regression model, CytoHubba plugin and expression validation. Co-expression correlation analysis was used to identify paired proteins for target genes, and a predictive model for pituitary adenoma invasiveness was constructed by target genes and paired proteins and assessed using ROC analysis, calibration curves and DCA. GO function, pathway (GSEA or GSVA) and immune cell analysis (ssGSEA or CIBERSORT) were further utilized to explore the action mechanism of target gene. Finally, immunohistochemistry and cell function experiments were used to detect the differential expression and key roles of the target genes in pituitary adenomas.

Results: Finally, Heat shock protein family D member 1 (HSPD1) was identified as a target gene. The quality of a predictive model for pituitary adenoma invasiveness consisting of HSPD1 and its paired protein expression profiles was satisfactory. Moreover, the expression of HSPD1 was significantly lower in invasive pituitary adenomas than in non-invasive pituitary adenomas. Downregulation of HSPD1 may be significantly related to invasion process, mitochondria-related pathway and immune cell regulation in pituitary adenomas.

Conclusion: The downregulation of HSPD1 may serve as a predictive indicator for identifying invasive pituitary adenomas.

Keywords: Diagnosis; HSPD1; Mitophagy, Invasion; Pituitary adenoma.