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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 \u201cmRNA processing\u201d and \u201cspindle organization\u201d biological processes are important in NFAPs invasiveness. Specifically, our results suggest\n                    <jats:italic>Nkx3-1 and Fech<\/jats:italic>\n                    as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-00431-2","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T06:13:12Z","timestamp":1634883192000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-8589","authenticated-orcid":false,"given":"Nasibeh","family":"Khayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Jalessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Jahanbakhshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Tabib khooei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mirzaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"issue":"suppl_4","key":"431_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noy131","volume":"20","author":"QT Ostrom","year":"2018","unstructured":"Ostrom, Q. 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