Clinical Study Of The Aggressiveness Of Pituitary Non-functional Adenoma And Analysis Of Transcriptomic Differences

Objective:To explore the clinical features of aggressive and recurrent pituitary nonfunctioning adenomas by analyzing the clinical data of patients with nonfunctioning adenomas.Methods:The clinical data of 480 patients who underwent transsphenoidal pituitary adenoma resection in Qilu Hospital of Shandong University from January 2018 to December 2020 were retrospectively analyzed.According to the Knosp grade,it was divided into invasive group and non-invasive group,and the corresponding clinical features,imaging manifestations and hormone levels of each group were analyzed.The main indicator of follow-up was whether there was recurrence,and further analysis of risk factors for recurrence.Results:1.General clinical data:A total of 480 patients with non-functioning pituitary adenoma were included in this study,including 228 males(47.5%)and 252 females(52.5%),with a male to female ratio of 1:1.11.The peak age of onset of nonfunctioning pituitary adenoma is between 40 and 60 years old.The mean maximum tumor diameter was 2.89 cm,and the median tumor maximum diameter was 2.80 cm.Among them,microadenomas accounted for 1%,macroadenomas accounted for 88.8%,and giant adenomas accounted for 10.2%.82.25%of the patients had optic chiasm compression.According to Knosp classification,there were 221 cases of non-invasive non-functioning adenomas(Knosp grade 0-2),accounting for 62%,and 161 cases of invasive non-functioning adenomas(Knosp grade 3-4),accounting for 38%.2.The clinical characteristics of invasive non-functional adenoma:the course of disease,maximum diameter of tumor,tumor volume,total surgical resection,optic nerve compression and surgical There was a statistical difference in pro-IGF-1 levels.There was no significant difference in age,gender,and first operation between the invasive non-functioning adenoma group and the non-invasive non-functioning adenoma group.In terms of preoperative hormone levels,only the preoperative IGF-1 level was higher in the invasive group than in the non-invasive group.There were differences between the sex groups,and there was no statistical difference in the preoperative levels of other GH,ACTH,PRL,LH,FSH,and TSH between the two groups.The rank sum test was used to compare the Ki-67 index between the two groups,and there was a significant statistical difference between the two groups.3.Clinical characteristics of recurrent nonfunctioning adenomas:480 patients were followed up,with an average follow-up time of 40.62 months,a minimum follow-up time of 25 months,and a maximum of 55 months.A total of 75 people were lost to follow-up,5 died,1 did not wake up after operation,59 relapsed,340 did not relapse,the recurrence rate was 14.79%.There were no significant differences in age,gender,KI-67 index,and optic nerve compression between the recurrence group and the non-relapse group.The preoperative pituitary axis hormone levels between the two groups were compared and analyzed.There was no significant difference in the levels of ACTH,IGF-1 and other pituitary axis hormones between the two groups.There were differences between the recurrent group and the non-recurrent group in the course of disease,the largest diameter of the tumor,the volume of the tumor,the surgical incomplete resection of the tumor,and whether the first operation or not.From the data analysis,the non-functioning pituitary adenomas in the recurrence group had a longer course of disease,larger tumor diameters and larger tumor volumes.Patients with incomplete surgical resection and non-first surgery are more likely to relapse.4.Risk factors for recurrence of nonfunctioning adenomas:Univariate logistic regression analysis indicated that course of disease,recurrence,maximum tumor diameter,tumor volume,degree of resection,and Knosp grade were all risk factors for recurrence of nonfunctioning pituitary adenomas.In order to avoid the influence of confounding factors,multivariate analysis was used to correct for confounding factors such as age and gender,indicating whether recurrence(P=0.000)and Knosp grade(P=0.043)were still related to recurrence after surgery.Conclusions:1.Aggressive non-functional adenoma has a longer course of disease,the maximum diameter and volume of the tumor are larger,the operation is not easy to completely resect,the optic nerve compression is more obvious,and the preoperative IGF-1 level is lower.2.Knosp classification,non-first surgery is an independent risk factor for predicting recurrence after surgery for non-functional adenomas.Objective: To construct RNA expression profiles by RNA sequencing of pituitary non-functional adenoma tissue.Analysis of differentially expressed RNA and further prediction of its function by bioinformatics analysis aimed at finding potential targets of invasion interest.Study Methods: Eight patients with non-ftmctioning pituitary tumors admitted to the Department of Neurosurgery of Qilu Hospital of Shandong University were included.After surgery,tissue was collected,and the differentially expressed inRNA,IncRNA and circRNA in tumor tissues of invasive and non-invasive patients were detected by RNA sequencing technology,and their biological functions were analyzed through GO and KEGG pathways to establish miRNA-circRNA-mRNA regulatory network.Results of the study: 1.According to the sequencing results,662 mRNAs were dysregulated in patients with invasive non-functional adenomas(337 up-regulated and 325down-regulated)compared with patients with non-invasive non-functional adenomas.A total of 660 differentially expressed IncRNAs(304 up-regulated and 356 down-regulated)were detected.A total of 15 differentially expressed circRNAs(4 up-regulated and 11down-regulated)were detected.2.GO enrichment analysis of the main biological processes including Janus kinase activity and breast duct development.KEGG pathway analysis showed that ErbB signaling pathway,signaling pathway and cell adhesion were the most abundant pathways for target genes.3.The circRNA-miRNA-mRNA regulatory network in this study,including 5 circRNAs,12 miRNAs and 176 mRNAs.hsa-miR-6089,hsa-miR-762,hsa-miR-1273g-3p,hsa-miR-1273 a play an important role in the ceRNA co-expression network associated with invasive and non-invasive non-functional adenomas.Conclusion: 1.Detection of differentially expressed RNA between invasive and non-invasive non-fimctional adenoma tissue specimens,which may play an important role in aggressiveness through the JAK2 signaling pathway,ErbB signaling pathway,and cell adhesion.2.Unreported miRNAs that may be associated with the aggressiveness of non-functional adenomas were found: hsa-miR-6089,hsa-miR-762,hsa-miR-1273g-3p,hsa-miR-1273 a,which can be used as potential non-functional adenoma aggressiveness prediction targets.