BackgroundComplete resection of invasive pituitary adenoma is usually difficult, resulting in a high recurrence rate. Therefore, it is needed to find potential diagnostic markers and therapeutic targets for invasive pituitary adenoma.MethodsWe collected samples from patients with invasive and non-invasive pituitary adenomas from Beijing Tiantan Hospital for protein extraction and quantitative analysis. We identified differential proteins (DEPs) by differential analysis of the two groups. The intersection of differential proteins related to invasion and epithelial-mesenchymal transition (EMT) in the GeneCards database was identified as EMT-DEPs. The protein network of EMT-DEPs was analyzed using the STRING database and Cytoscape software, and the hub EMT-DEPs were obtained by the MCC algorithm of the cytoHubba plugin. Correlation analysis was used to obtain the interpairing proteins among EMT-DEPs, and core EMT-DEPs were identified based on the number of paired proteins. The Venn program was used to identify the intersection of hub EMT-DEPs and core EMT-DEPs as key EMT-DEPs. Finally, a series of analyses plus experiments were used to verify the correlation of the target protein with invasion and EMT in pituitary adenoma.ResultsQuantitative comparison of proteins between invasive and non-invasive pituitary adenomas indicated 833 differential proteins. The overlaps of EMT-related proteins and differential proteins consisted of 46 EMT-DEPs. There were 6 intersections between the hub EMT-DEPs and core EMT-DEPs. Using quantitative protein data and GSE169498 chip, we found that solute carrier family 2 member 1 (SLC2A1) was our target protein. SLC2A1 was significantly correlated with the invasiveness of pituitary adenoma, and the ROC curve was satisfactory. The functions and pathways of SLC2A1 and paired protein enrichment were closely linked to the EMT. Consistently, SLC2A1 expression was significantly and positively correlated with the expression of classical markers of EMT. The final experiment revealed that SLC2A1 was significantly upregulated in invasive pituitary adenoma.ConclusionSLC2A1 is significantly upregulated in invasive pituitary adenoma with satisfactory predictive value. It may regulate EMT. It may be a potential diagnostic marker for invasive pituitary adenoma.

OBJECTIVE There are few published data concerning pituitary adenomas (PAs) derived from multiple lineages. In this study the authors aimed to determine the clinicopathological characteristics and prognostic profiles of PAs with multiple cell lineage combinations (PAwMCs). METHODS The authors reviewed data on 723 patients with PAs who had undergone surgery between 2018 and 2021 and identified 93 cases (12.9%) of PAwMC. They collected detailed data on these cases, including clinical information, pathological features, and prognosis. From among 589 cases of PAs with only one cell lineage (PAwOCs), they randomly selected 100 cases to investigate differences between the two tumors. To enable investigation of the characteristics of different subgroups, they further subclassified PAwMCs into 4 groups according to the following specified combinations of pituitary-associated transcription factors: group A, immunopositive for pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor 1 (SF1); group B, immunopositive for Pit1 and T-box transcription factor (Tpit); group C, immunopositive for SF1 and Tpit; and group D, immunopositive for Pit1, SF1, and Tpit. RESULTS Compared with PAwOC, PAwMC was more often associated with hormone hypersecretion (31.0% vs 50.0%, p = 0.037) and had worse short-term prognoses with lower complete response rates (58.7% vs 30.0%, p = 0.026) and more postoperative complications (19.4% vs 35.9%, p = 0.041). Each of the 4 PAwMC subgroups had its own clinical features. Overall, PAwMCs displayed more neurological manifestations than evidence of hypersecretion, which may be attributable to a disparity between pituitary-associated transcription factors and endocrine-related manifestations. Moreover, multiple cell lineages, tumor size (p = 0.011), and Knosp grade (p = 0.013) were all found to be critical predictors of the prognosis of PAwMC. CONCLUSIONS The authors described a special subtype of PAs, which derived from multiple lineages. They found a unique effect of the combination of distinct cell lineages on PAs and present detailed clinicopathological and prognostic profiles of these special PAs. These data will contribute to a more comprehensive view of PAs and assist in the selection of treatment.

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