Single-cell and spatial transcriptomic analyses reveal heterogeneity characteristics and specific cell subtype regulators in growth hormone-secreting pituitary adenomas

Yu Zhang; Lifeng Wang; Xingcheng Yi; Xin Ma; Hongyu Wu; Mingzhao Zhang; Zhenqi Yang; Lizhen Ma; Zenghua Mi; Weijia Zhi; Cong Fu; Pinan Liu; Zhijun Yang

doi:10.1097/JS9.0000000000002178

Single-cell and spatial transcriptomic analyses reveal heterogeneity characteristics and specific cell subtype regulators in growth hormone-secreting pituitary adenomas

Int J Surg. 2024 Dec 31. doi: 10.1097/JS9.0000000000002178. Online ahead of print.

Authors

Yu Zhang¹, Lifeng Wang², Xingcheng Yi³, Xin Ma¹, Hongyu Wu¹, Mingzhao Zhang², Zhenqi Yang², Lizhen Ma², Zenghua Mi¹, Weijia Zhi², Cong Fu^{4

5}, Pinan Liu^{1

6}, Zhijun Yang¹

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Beijing Institute of Radiation Medicine, Beijing, China.
³ Laboratory of Cancer Precision Medicine, First Hospital of Jilin University, Changchun, Jilin, China.
⁴ Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China.
⁵ National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Jilin University, Changchun, Jilin, China.
⁶ Department of Neural Reconstruction, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China.

PMID: 39784532
DOI: 10.1097/JS9.0000000000002178

Abstract

Background: Growth hormone-secreting pituitary adenomas (GHPA) display diverse biological behaviors and clinical outcomes, necessitating the identification of tumor heterogeneity and prognostically relevant markers.

Methods: In this study, we performed single-cell RNA sequencing (scRNA-seq) on 10 GHPA samples, four of which also underwent spatial transcriptome sequencing, and used scRNA-seq data from four normal pituitary samples as controls. Cell subtype characterization in GHPA was analyzed using multiple algorithms to identify malignant bias regulators, which were then validated using a clinical cohort.

Results: We constructed the first single-cell and spatial transcriptome profiles of GHPA, which contained 87,862 cells and revealed 16 tumor cell subtypes. Among the tumor cells, we identified distinct developmental trajectories and three malignant-biased subtypes (PIT1_C05, PIT1_C06, and PIT1_C10). The spatial distribution characteristics of these malignant-biased cells may influence the growth characteristics and prognosis of GHPA. We screened specific regulatory transcription factors, including FOXO1, GTF2IRD1, and MAX. Clinical cohort validation indicated that FOXO1 might be associated with tumor invasion and progression, while high expression of MAX could result in poor endocrine outcomes.

Conclusion: GHPA exhibits rich heterogeneity and diverse cell subtypes, with specific transcription factors potentially regulating cell malignant bias, thereby influencing tumor characteristics and prognosis.