Integrated multi-omics profiling of nonfunctioning pituitary adenomas

Wei, Zhenqing; Zhou, Cuiqi; Li, Minghui; Huang, Ruocheng; Deng, Hongjuan; Shen, Stephen; Wang, Renzhi

doi:10.1007/s11102-020-01109-0

Cited by 7 publications

(5 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mTOR signaling pathway was significant based on the GSVA analysis of the contrast between the two subclusters. Neuroactive ligand–receptor interaction and calcium signaling pathway have been found in NF-PitNETs, and they have been revealed to be possibly associated with tumor progression [ 44 , 45 ], further validating the results of the present study. CCL17 secreted by tumor-associated macrophages could promote pituitary adenoma invasion by enhancing the mTORC1 signaling pathway [ 46 ].…”

Section: Discussionsupporting

confidence: 89%

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration

Feng,

Hou,

et al. 2023

Lipids Health Dis

View full text Add to dashboard Cite

Objective This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs. Methods First, a retrospective analysis of single-center clinical data was performed. Second, the immune cell infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism-related genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed. Results The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol (P = 0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found three immune cells between invasive and noninvasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. The chi-square test revealed that the two subgroups had statistically significance in the invasive and noninvasive samples (P = 0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand–receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison. Conclusion By clinical data and bioinformatics analysis, cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.

show abstract

Section: Discussionsupporting

confidence: 89%

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration

Feng,

Hou,

et al. 2023

Lipids Health Dis

View full text Add to dashboard Cite

show abstract

“…Quantitative proteomics using two dimensional liquid chromatography-tandem mass spectrometry revealed the expression of EphA10, EFNA5 and EFNB1 in NF-PitNETs [ 36 ]. Comparison of highly proliferative NF-PitNETs versus NF-PitNETs suggested differential gene expression of EPH receptor signaling pathway [ 45 ] which similarly was found hypomethylated in re-intervention versus stable NF-PitNET patients [ 37 ]. Transcriptome analysis of PitNETs identified upregulation of EphB6 in silent ACTH PitNETs, gonadotrophinomas and null cell PitNETs when clustered together and of EphA4 in ACTH-secreting PitNETs [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Prolactin secreting pituitary neuroendocrine tumors (PitNETs) are the most common pituitary tumors (50%) followed by non-functioning pituitary neuroendocrine tumors (NF-PitNETs) comprising ~ 30% of PitNETs [ 35 ]. Dysregulated expression of Eph family members in NF-PitNETs was reported or may be obtained from several reports as part of broad gene expression profiling of PitNETs [ 36 – 45 ]. In this study we aimed to examine the expression of EphB6 in PitNETs.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size

Rubinfeld,

Cohen,

Bendavid

et al. 2024

Mol Biol Rep

View full text Add to dashboard Cite

Background Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors. Methods and Results Human normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size. Conclusions Our results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis.

show abstract

“…The mTOR signaling pathway was signi cant based on the GSVA analysis of the contrast between the two sub-clusters. Neuroactive ligand-receptor interaction and calcium signaling pathway have been found in NF-PitNETs, and they have been revealed to be possibly associated with tumor progression [44,45],…”

Section: Discussionmentioning

confidence: 99%

Identification of cholesterol metabolism-related subtypes in Nonfunctioning Pituitary neuroendocrine tumors and analysis of immune infiltration

feng

Hou

Fang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective: This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumor (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs. Methods: First, a retrospective analysis of single-center clinical data was performed. Second, the immune infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed. Results: The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol(P=0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, Cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found 3 immune cells between invasive and non-invasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. Chi-square test revealed that the two subgroups had statistically significance in the invasive and non-invasive samples (P=0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand–receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison. CONCLUSION: By clinical data and bioinformatics analysis, Cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.

show abstract

Integrated multi-omics profiling of nonfunctioning pituitary adenomas

Cited by 7 publications

References 63 publications

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration

Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size

Identification of cholesterol metabolism-related subtypes in Nonfunctioning Pituitary neuroendocrine tumors and analysis of immune infiltration

Contact Info

Product

Resources

About