Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness

Abstract

Non-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that “mRNA processing” and “spindle organization” biological processes are important in NFAPs invasiveness. Specifically, our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps

“…The random forest algorithm offers various metrics for assessing variable importance, among which Mean Decrease Accuracy (MDA) is considered the most reliable. MDA determines importance by evaluating the reduction in classification accuracy when the expression values of a particular gene are randomly permuted 18 , 19 . In our study, we utilized MDA to identify the important switch genes, as presented in Fig.…”

“…So far, the three-way interaction approach has been employed to deciphering the pathogenesis of several diseases, including inflammatory diseases 18 , 19 . The importance of RT-DOb /{ Csf1r , Milr1 } triplet in onset of Alzheimer’s disease has been suggested and validated in previous studies.…”

FECH Expression Correlates with the Prognosis and Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma

“…Relevant studies have shown that changes in FECH expression were detected in human colon cancers and that loss of FECH has a tumor-suppressive effect on colon carcinogenesis in vitro [ 26 ], which was a potential tumor-suppressor gene for colon cancer [ 27 ]. The FECH gene may be a switch gene involved in the invasiveness of pituitary nonfunctioning adenomas [ 28 ].…”

RT-DOb, a switch gene for the gene pair {Csf1r, Milr1}, can influence the onset of Alzheimer’s disease by regulating communication between mast cell and microglia

“…Previously, putative switch mechanisms involved in triggering Alzheimer's disease (AD) were detected using a three-way interaction model [10]. Use of three-way interaction models, including the liquid association model that was used in the earlier study, is an efficient approach for finding switch mechanisms [10][11][12][13][14]. In this model, it is assumed that there is a switch gene, say Z, which controls the co-expression of a gene pair, say {X 1 and X 2 }.…”