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Abstract Pituitary neuroendocrine tumors (PitNETs) are one of the most common intracranial tumors with diverse clinical manifestations. Current pathological classification systems rely primarily on histological hormone staining and transcription factors (TFs) expression. While effective in identifying three major lineages, molecular characteristics based on hormones and TFs lack sufficient resolution to fully capture the complex tumor heterogeneity. Transcriptional diversity by alternative splicing (AS) offered additional insight to address this challenge. Here, we perform bulk and full-length single-cell RNA sequencing to comprehensively investigate AS dysregulation across all PitNET lineages. We reveal pervasive splicing dysregulations that better depict tumor heterogeneity. Additionally, we delineate fundamental splicing heterogeneity at single-cell resolution, confirming bulk findings and refining splicing dysregulation varying among tumor cell types. Notably, we effectively distinguish the silent corticotroph subtype and define a distinct TPIT lineage subtype, which is associated with worse clinical outcomes and increased splicing abnormalities driven by altered ESRP1 expression. In conclusion, our results characterize the subtype specific AS landscape in PitNETs, enhancing the understanding of the PitNETs subtyping.

Abstract Background Depression and anxiety significantly impact the quality of life in individuals with Cushing’s disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology. Results The gut bacterial phenotype of patients with Cushing’s disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2–14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing’s disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing’s disease with different levels of depression and anxiety. Conclusions In summary, this research enhances our current understanding of how gut microbes in patients with Cushing’s disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract

Abstract Background Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood. Methods In this study, we performed integrative spatial transcriptomics (ST) and single‐cell RNA sequencing (scRNA‐seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics. Results By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNVhigh and CNVlow areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNVhigh area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment. Conclusion In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA‐seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs. Key points The first‐ever visualization of cellular distributions in normal and tumor pituitary tissues. The inter‐ and intra‐tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed. Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.

IntroductionCognitive impairment is a frequent clinical symptom of non-communicating hydrocephalus (NCH) involving multiple domains, including executive function, working memory, visual-spatial function, language, and attention. Functional magnetic resonance imaging (fMRI) can be used to obtain information on functional activity in local brain areas and functional connectivity (FC) across multiple brain regions. However, studies on the associated cognitive impairment are limited; further, the pathophysiological mechanisms of NCH with cognitive impairment remain unclear. Here, we aimed to explore alterations in regional neural activity and FC, as well as the mechanisms of cognitive impairment, in patients with NCH.MethodsOverall, 16 patients with NCH and 25 demographically matched healthy controls (HCs) were assessed using the Mini-Mental State Examination (MMSE) and fMRI. Changes in regional homogeneity (ReHo), degree centrality (DC), and region of interest-based FC were analyzed in both groups. The relationship between fMRI metrics (ReHo, DC, and FC) and MMSE scores in patients with NCH was also investigated.Results and discussionCompared with the HC group, the NCH group exhibited significantly lower ReHo values in the left precentral and postcentral gyri, and significantly higher ReHo values in the left medial prefrontal cortex (MPFC). The NCH group also showed significantly higher DC values in the bilateral MPFC compared with the HC group. Regarding seed-based FC, the MPFC showed reduced FC values in the right superior parietal and postcentral gyrus in the NCH group compared with those in the HC group. Moreover, within the NCH group, MMSE scores were significantly negatively correlated with the ReHo value in the left MPFC and the DC value in the bilateral MPFC, whereas MMSE scores were significantly positively correlated with FC values. To conclude, regional neural activity and FC are altered in patients with NCH and are correlated with cognitive impairment. These results advance our understanding of the pathophysiological mechanisms underlying the association between NCH and cognitive impairment.

Abstract Background Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. Methods We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. Results We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. Conclusions Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.

Abstract Background The three‐dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored. Methods We employed Hi‐C and RNA‐seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns. Results We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi‐C and RNA‐seq data demonstrated that changes inhigher‐order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/β‐Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT‐PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro. Conclusion Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.

Abstract Purpose Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function. Methods A systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE. Results Sixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95% CI, 0.622–0.703; P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95% CI, 0.503–0.620; P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator’s definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95% CI, 0.527–0.961; P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95% CI, 0.393–0.746; P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95% CI, 0.022–0.783; P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant. Conclusions In patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.

The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central nervous system through the microbiome-brain-gut axis in the past ten years. As more and more research has been done on the relationship between the disease of the central nervous system and gut microbes. This fact is being revealed that gut microbes seem to play an important role from the onset and progression of the disease to clinical symptoms, and new treatments. As a special tumor of the central nervous system, pituitary neuroendocrine tumors (PitNETs)are closely related to metabolism, endocrinology, and immunity. These factors are the vectors through which intestinal microbes interact with the central nervous system. However, little is known about the effects of gut microbes on the PitNET. In this review, the relationship of gut microbiota in PitNETs is introduced, the potential effects of the gut-brain axis in this relationship are analyzed, and future research directions are presented.

ObjectiveTo investigate the clinical and pathological factors associated with preoperative hypothalamus invasion and postoperative outcomes of adamantinomatous craniopharyngiomas (ACPs) after the expanded endonasal approach (EEA) resection.MethodsNinety-three specimens of ACPs, consisting of 71 primary and 22 recurrent tumors, were investigated for the expression of TGF-β1, SMAD2, SMAD3, and β-catenin by immunohistochemistry staining. The clinical information of relevant patients, including the extent of resection, hypothalamus invasion, endocrinopathy, complications, and prognosis, was reviewed. The relationships between the expression of these immunopathological markers and clinical factors were analyzed.ResultsEndocrinological dysfunctions were more common in recurrent patients and primary patients with hypothalamus invasion in the comparisons. For recurrent patients, the rate of gross total resection (GTR) was significantly lower than for primary patients (63.6% vs. 90.1%, P = 0.007). According to radiological and intraoperative findings, invasive ACPs (IACPs) included 48 (67.6%) cases in primary tumors. The expression of TGF-β1 and β-catenin was significantly higher in recurrent tumors (P = 0.021 and P = 0.018, respectively) and IACPs (P = 0.008 and P = 0.004, respectively). The expression level of TGF-β1 was associated with hypothalamus involvement (Puget grade, P = 0.05; Vile grade, P = 0.002), postoperative endocrinopathy (P = 0.01), and pituitary stalk preservation (P = 0.008) in primary patients. In addition, the extent of resection, treatment history, hypothalamic invasion, and level of TGF-β1 expression had significant influences on tumor recurrence/progression after surgery separately.ConclusionOur study demonstrated the potential role of TGF-β1 in the regulation of hypothalamus invasion in ACPs and the prediction of prognosis after EEA surgery. The TGF-β signaling pathway may represent a crucial mechanism in the aggressive behavior and progression of ACPs.

IntroductionThe invasive behavior of nonfunctioning pituitary neuroendocrine tumors (NF-PitNEts) affects complete resection and indicates a poor prognosis. Cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The current study aimed to screen the key immune-related genes in NF-PitNEts with invasion.MethodsWe used two cohorts to explore novel biomarkers in NF-PitNEts. The immune infiltration-associated differentially expressed genes (DEGs) were obtained based on high/low immune scores, which were calculated through the ESTIMATE algorithm. The abundance of immune cells was predicted using the ImmuCellAI database. WGCNA was used to construct a coexpression network of immune cell-related genes. Random forest analysis was used to select the candidate genes associated with invasion. The expression of key genes was verified in external validation set using quantitative real-time polymerase chain reaction (qRT‒PCR).ResultsThe immune and invasion related DEGs was obtained based on the first dataset of NF-PitNEts (n=112). The immune cell-associated modules in NF-PitNEts were calculate by WGCNA. Random forest analysis was performed on 81 common genes intersected by immune-related genes, invasion-related genes, and module genes. Then, 20 of these genes with the highest RF score were selected to construct the invasion and immune-associated classification model. We found that this model had high prediction accuracy for tumor invasion, which had the largest area under the receiver operating characteristic curve (AUC) value in the training dataset from the first dataset (n=78), the self-test dataset from the first dataset (n=34), and the independent test dataset (n=73) (AUC=0.732/0.653/0.619). Functional enrichment analysis revealed that 8 out of the 20 genes were enriched in multiple signaling pathways. Subsequently, the 8-gene (BMP6, CIB2, FABP5, HOMER2, MAML3, NIN, PRKG2 and SIDT2) classification model was constructed and showed good efficiency in the first dataset (AUC=0.671). In addition, the expression levels of these 8 genes were verified by qRT‒PCR.ConclusionWe identified eight key genes associated with invasion and immunity in NF-PitNEts that may play a fundamental role in invasive progression and may provide novel potential immunotherapy targets for NF-PitNEts.

BackgroundTraditionally, supratentorial craniotomy has been used to sever tuberculum sellae meningiomas (TSMs), but there has been a remarkably increasing tendency of extended endoscopic endonasal approach (EEEA) used to treat TSMs in the recent decade. Several documents have described the advantages and disadvantages of both approaches, but there is no consensus on whether one is superior to the other.ObjectiveThis study aimed to compare surgical outcomes between craniotomy and EEEA for TSMS treated at our institution.MethodsFrom January 2015 to December 2021, a total of 84 cases of TSMs were included in this study. Cases were separated into two groups: the craniotomy group and the EEEA group. Their anamneses and surgical records were reviewed. Demographic data, presenting symptoms, tumor volume, extent of resection, visual outcomes, and follow-up data were tabulated. The Kaplan–Meier curves were constructed for the PFS for both cohorts.ResultsComplete data were available for 84 surgeries; 39 cases were treated via craniotomy, and 45 were treated via EEEA. Patient demographic data, pre-operative symptoms, and tumor characteristics were similar between the two cohorts. The extent of resection was similar between the two groups (GTR: 91.11% EEEA vs. 87.18% craniotomy; STR 8.89 vs. 12.82%, p = 0.91). There was no difference in visual outcomes between both groups (92.1 vs. 84.84%, p = 0.46). An increased rate of cranial nerve injury was noted in the craniotomy group (0 vs. 10.25%, p = 0.04). Post-operative CSF leak rate occurred in one patient in the EEEA group. The PFS curves (p = 0.52) and recurrence/progression rates (13.33 vs. 20.51%, p = 0.39) were similar between the two groups.ConclusionBoth EEEA and craniotomy can successfully sever TSMs. The recurrence/progression rate and PFS appear to be similar between the two groups. Although there are no differences in EOR and visual outcomes between the two groups, there was a clear trend in the EEEA group to obtain a better outcome. CSF leakage was common in the EEEA cohort, whereas the rate of cranial nerve injury was found to be higher in the craniotomy cohort. We believe that our data support the conclusion that EEEA surgery is the preferred approach for the removal of TSMs.

BackgroundThe systemic inflammation score (SIS), based on preoperative lymphocyte to monocyte ratio (LMR) and albumin (ALB), was recently developed and is demonstrated to be a novel prognostic indicator in several cancers. However, data discussing the utility of SIS in chordoma are lacking. We aimed to investigate the distribution and the prognostic role of SIS in primary skull base chordoma patients undergoing surgery.Material and methodsPreoperative SIS was retrospectively collected from 183 skull base chordoma patients between 2008 and 2014 in a single center. Its associations with clinical features and overall survival (OS) were further analyzed. The SIS-based nomogram was developed and evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsThe numbers of patients in the SIS 2, 1, and 0 group were 29 (15.8%), 60 (32.8%), 94 (51.4%), respectively. High SIS was associated with older age (p = 0.008), brainstem involvement of tumors (p = 0.039), and adverse OS (p < 0.001). Importantly, multivariate Cox analysis showed that high SIS independently predicts adverse OS. Furthermore, the nomogram based on SIS and clinical variables showed eligible performance for OS prediction in both training and validation cohorts.ConclusionsThe SIS is a promising, simple prognostic biomarker, and the SIS-based nomogram serves as a potential risk stratification tool for outcome in skull base chordoma patients.

ObjectiveTo determine risk factors and management for the development of a postoperative cerebrospinal fluid (CSF) leak after an endoscopic endonasal surgery (EES) for pituitary adenomas.MethodsThe clinical data of 400 patients who underwent EES for resection of pituitary adenomas from December 2018 to November 2019 in the Department of Neurosurgery of Beijing Tiantan Hospital were retrospectively reviewed. Age, gender, body mass index (BMI), tumor size, Knosp grade, suprasellar extension grade, sellar floor erosion grade, repeated transsphenoidal surgery, intraoperative CSF leak, use of pedicled nasoseptal flap and lumbar drain were collected and analyzed.ResultsPostoperative CSF leak occurred in 14 of 400 patients (3.5%). Age, gender, BMI, tumor size, Knosp grade and repeated transsphenoidal surgery were not risk factors for CSF leak. Suprasellar extension grade (≥B 6.0% vs.

PurposeTumor consistency is important for pituitary neuroendocrine tumors (PitNETs) resection to improve surgical outcomes. In this study, we evaluated the T2-WI of PitNETs and defined a specific T2-WI signaling manifestation, the “Mosaic sign,” to predict tumor consistency and resection of PitNETs.DesignA retrospective review of MRI and tumor histology of 137 consecutive patients who underwent endoscopic endonasal resection for PitNETs was performed.MethodsThe “Mosaic sign” was defined by the ratio of the tumor itself T2-WI signals, and characterized by multiple intratumor hyperintense dots. The degree of tumor resection was an assessment by postoperative MRI examination. The presence of the “Mosaic sign” was compared with patients' basic information, tumor consistency, tumor pathological staining, and surgical result. To determine whether the presence or absence of “Mosaic sign” could predict tumor consistency and guide surgical resection of tumors.ResultsStatistical analysis showed that the consistency of the tumor and the degree of resection were correlated with the “Mosaic sign”. In the 137 cases of T2-WI, 43 had “Mosaic sign”, 39 cases had soft tumor consistency, and 4 were classified as fibrous, of which 42 were completely resected and 1 was subtotal resected. Of the 94 patients without “Mosaic sign”, the consistency of tumor of 54 cases were classified as soft, the remaining 40 cases were fibrous, 80 cases were completely resected, and 14 cases were subtotal resected. Postoperative cerebrospinal fluid leakage occurred in 1 patient. The number of corticotroph adenomas in the group of “Mosaic sign” was higher, with the statistical difference between the two groups (P = 0.0343).ConclusionsThe presence of the “Mosaic sign” in T2-WI may provide preoperative information for pituitary adenomas consistency and effectively guide surgical approaches.

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p

ObjectAlthough revision surgery for recurrent craniopharyngiomas is more challenging than primary surgery and often accompanies a higher risk of death and complications, endoscopic endonasal transsphenoidal surgery (EETS) is sometimes still an effective and reliable treatment option. In this study, we introduced the surgical outcomes of EETS for recurrent craniopharyngiomas and summarized the surgical experiences.MethodsBetween 2014 and 2018, 28 patients with recurrent craniopharyngiomas underwent 29 EETS in our department. We regarded the patient undergoing two EETS as two independent patients in statistical analysis. Of the 29 patients, 16 had undergone 1 previous surgery, 10 had undergone 2 previous surgeries, and the remaining 3 patients had undergone 3 surgeries. The extent of resection, visual and endocrine outcomes, and complications of all the patients were collected and analyzed.ResultsGross total resection was accomplished in 16 patients (55.17%), subtotal resection in 11 patients (37.93%), and partial resection in 2 patients (6.9%). Among the 22 patients with preoperative visual acuity and visual field impairment, some degree of vision improvement was observed in 18 patients, 3 patients were without visual change, and perpetual deterioration of vision occurred in one patient. The remaining six patients had normal vision before and after surgery. Postoperative endocrine tests showed that, among five patients with normal preoperative pituitary hormone function, only one patient still had normal pituitary hormone function and the other four patients had one or more hypothalamic-pituitary axes involved. None of the patients with preoperative endocrine dysfunction had endocrine function improved. Diabetes insipidus was observed in six new cases postoperatively. Cerebrospinal fluid (CSF) leakage occurred in 1 patient. One patient had bacterial meningitis, which was cured with antibiotics and a lumbar drain. No serious morbidity and mortality occurred in all patients.ConclusionsFor recurrent craniopharyngiomas, a personalized treatment plan should be developed according to the tumor characteristics and the patient's situation. There is no omnipotent method to be used for all patients. The EETS still is a safe and effective way to treat recurrent craniopharyngiomas in appropriate patients.

Background and Objectives: The diagnosis and treatment of pituitary adenomas with cavernous sinus invasion pose significant challenges for clinicians. The objective of this study is to investigate the expression profile and prognostic value of HSPB1 (heat shock protein beta-1) in pituitary adenomas with invasive and non-invasive features. Additionally, we aim to explore the potential relationship between HSPB1 expression and immunological functions in pituitary adenoma. Materials and Methods: A total of 159 pituitary adenoma specimens (73 invasive tumours and 86 non-invasive tumours) underwent whole-transcriptome sequencing. Differentially expressed genes and pathways in invasive and non-invasive tumours were analysed. HSPB1 was subjected to adequate bioinformatics analysis using various databases such as TIMER, Xiantao and TISIDB. We investigated the correlation between HSPB1 expression and immune infiltration in cancers and predicted the target drug of HSPB1 using the TISIDB database. Results: HSPB1 expression was upregulated in invasive pituitary adenomas and affected immune cell infiltration. HSPB1 was significantly highly expressed in most tumours compared to normal tissues. High expression of HSPB1 was significantly associated with poorer overall survival. HSPB1 was involved in the regulation of the immune system in most cancers. The drugs DB11638, DB06094 and DB12695 could act as inhibitors of HSPB1. Conclusions: HSPB1 may serve as an important marker for invasive pituitary adenomas and promote tumour progression by modulating the immune system. Inhibitors of HSPB1 expression are currently available, making it a potential target for therapy in invasive pituitary adenoma.

The clinical diagnosis and treatment of pituitary neuroendocrine tumors (PitNETs) that invade the cavernous sinus are fraught with difficulties and challenges. Exploring the biological characteristics involved in the occurrence and development of PitNETs that invade the cavernous sinus will help to elucidate the mechanism of cavernous sinus invasion. There are differences between intrasellar tumors (IST) and cavernous sinus-invasion tumors (CST) in ultramicrostructure, tumor microenvironment (TME), gene expression, and signaling pathways. The microvascular endothelial cell is increased in CST. The VEGFR signaling pathway, VEGF signaling pathway, and chemokine signaling pathway are activated in CST. HSPB1 is upregulated in CST and promotes cell proliferation, cell viability, and migration. HSPB1 promotes the release of VEGF from GT1-1 cells and activates the VEGF signaling pathway in bEnd.3 cells. HSPB1 promotes the migration of bEnd.3 cells to GT1-1 cells and promotes the formation of blood vessels of bEnd.3 cells. bEnd.3 cells can release CCL3 and CCL4 and promote the vitality, proliferation, and migration of GT1-1 cells. HSPB1 promotes the formation of blood vessels of bEnd.3 cells and ultimately leads to tumor growth in vivo. HSPB1 acts as a key gene for invasion of the cavernous sinus in PitNETs, remodeling TME by promoting the formation of blood vessels of brain microvascular endothelial cells. The synergistic effect of tumor cells and microvascular endothelial cells promotes tumor progression. The mechanism by which HSPB1 promotes tumor invasion by inducing angiogenesis in PitNETs may be a new target for the treatment of PitNETs invading the cavernous sinus. [ABSTRACT FROM AUTHOR]