Screening and Identification of Key Microenvironment-Related Genes in Non-functioning Pituitary Adenoma.

Jing Guo,Yazhuo Zhang,Yulou Liu,Chuzhong Li,Weiyan Xie,Qiuyue Fang

doi:10.3389/fgene.2021.627117

Abstract

PurposeNon-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor, which can be locally invasive and can have a high recurrence rate. The tumor microenvironment (TME) shows a high correlation with tumor pathogenesis and prognosis. The current study aimed to identify microenvironment-related genes in NFPAs and assess their prognostic value.Methods73 NFPA tumor samples were collected from Beijing Tiantan Hospital and transcriptional expression profiles were obtained through microarray analysis. The immune and stromal scores of each sample were calculated through the ESTIMATE algorithm, and the patients were divided into high and low immune/stromal score groups. Intersection differentially expressed genes (DEGs) were then obtained to construct a protein–protein interaction (PPI) network. Potential functions and pathways of intersection DEGs were then analyzed through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The prognostic value of these genes was evaluated. The quantitative real-time polymerase chain reaction in another set of NFPA samples was used to confirm the credibility of the bioinformatics analysis.ResultsThe immune/stromal scores were significantly correlated with cavernous sinus (CS) invasion. The Kaplan–Meier curve indicated that the high immune score group was significantly related to poor recurrence-free survival. We identified 497 intersection DEGs based on the high vs. low immune/stromal score groups. Function enrichment analyses of 497 DEGs and hub genes from the PPI network showed that these genes are mainly involved in the immune/inflammatory response, T cell activation, and the phosphatidylinositol 3 kinase-protein kinase B signaling pathway. Among the intersection DEGs, 88 genes were further verified as significantly expressed between the CS invasive group and the non-invasive group, and five genes were highly associated with NFPA prognosis.ConclusionWe screened out a series of critical genes associated with the TME in NFPAs. These genes may play a fundamental role in the development and prognosis of NFPA and may yield new therapeutic targets.

Highlights

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms
The stromal scores ranged from −1648.8 to 1273.7, the immune scores ranged from −1429.1 to 2376.3, and the ESTIMATE scores ranged from −2866 to 3650, as calculated using the ESTIMATE algorithm
The distribution of the immune and stromal scores did not vary by histological subtype (p = 0.84/0.16) and tumor size (p = 0.68/0.75) but was significantly different from that of the Cavernous sinus (CS) invasive and CS noninvasive groups (p = 0.0057/0.0013) (Figures 1A,B)

Summary

Introduction

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms. They account for 14–54% of pituitary adenomas, which are the second most common primary intracranial tumor (Fontana and Gaillard, 2009; Fernandez et al, 2010; Ostrom et al, 2015; Day et al, 2016; Ntali and Wass, 2018). Apart from pituitary incidentalomas, NFPAs are usually detected when the tumor is large enough to cause pressure effects on surrounding structures, with symptoms including headache, visual field defects, decreased libido and hydrocephalus (Lindholm et al, 2006; Sam et al, 2015). NFPAs are benign neoplasms, most demonstrate invasive growth at the time of diagnosis, manifesting as local infiltration, and have an increased risk of post-operative recurrence (Landeiro et al, 2015).

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Conclusion