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

in International journal of surgery (London, England) by 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

TLDR

  • The study used single-cell RNA sequencing to identify 16 tumor cell subtypes in GHPA, including three malignant-biased subtypes, and validated findings in a clinical cohort.

Abstract

Growth hormone-secreting pituitary adenomas (GHPA) display diverse biological behaviors and clinical outcomes, necessitating the identification of tumor heterogeneity and prognostically relevant markers. 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. 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. GHPA exhibits rich heterogeneity and diverse cell subtypes, with specific transcription factors potentially regulating cell malignant bias, thereby influencing tumor characteristics and prognosis.

Overview

  • The study aimed to identify tumor heterogeneity and prognostically relevant markers in growth hormone-secreting pituitary adenomas (GHPA) using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing.
  • The study analyzed 10 GHPA samples, four of which underwent spatial transcriptome sequencing, and compared them to four normal pituitary samples.
  • The primary objective was to characterize GHPA cell subtypes and identify malignant-biased regulators using scRNA-seq data and validate the findings in a clinical cohort.

Comparative Analysis & Findings

  • The study identified 16 tumor cell subtypes in GHPA, including three malignant-biased subtypes (PIT1_C05, PIT1_C06, and PIT1_C10) that displayed distinct developmental trajectories.
  • The spatial distribution of these malignant-biased cells may influence the growth characteristics and prognosis of GHPA.
  • FOXO1 was found to be associated with tumor invasion and progression, while high expression of MAX was linked to poor endocrine outcomes in a clinical cohort validation

Implications and Future Directions

  • The study highlights the importance of analyzing tumor heterogeneity in GHPA to better understand the relationship between cell subtypes and clinical outcomes.
  • Future research could focus on developing therapies targeting specific transcription factors, such as FOXO1 and MAX, to improve treatment outcomes for GHPA patients.
  • The study's findings could also inform the development of novel biomarkers for GHPA diagnosis and prognosis.
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