Preliminary Study On The Association Between RN41 Expression And Tumor Invasiveness In Nonfunctional Pituitary Adenomas

Background:Pituitary adenoma is the 3rd most frequent endocranial tumor,which is accounted for about 15%.And non-functional pituitary adenoma(NFPA)accounts for20%of all pituitary adenoma.The invasiveness of NFPA is a key factor which affecting the surgical results and recurrence-free survival.It is uneasy to cut all tumor off for invasive NFPA.And the patient who suffer it has a high recurrence rate after tumor resection operated.Ring finger protein(RNF41)is a kind of ubiquitin ligase,which was designed for binding to a series of intracellular protein to regulate cellular proliferation and apoptosis.This protein showed great value and became a hotspot of the mechanism of development in carcinoma.Objects:Our aim is to investigate and the relevance between NFPA invasiveness and RNF41 expression at first.After then we are to analysis the correlation between RNF41expression and other common protein of ubiquitination pathway.with all these work we are trying to preliminarily reveal the possible inner relationship of the mechanism in NFPA invasiveness development.Methods:1.The paraffin specimens were collected from operated patients in the Affiliated Hospital of Qingdao University in 2013～2016.With RNF41 expression checked by immunohistochemical method,all patients’clinical data and statistical methods,the correlation of RNF41 expression and tumor invasiveness,recurrence-free survival was analyzed.2.With collecting paraffin specimens from operated patients in the Affiliated Hospital of Qingdao University in 2019～2021,the RNF41,HER2,HER3,MDM2 and P53expression was checked by immunohistochemical method.All specimens was divided into two groups,such as invasive group and non-insvasive group.With statistical method used,the expression difference between the two groups and the correlation between all protein were analyzed.Results:1.The analysis of 50 collected patients showed that the invasiveness of NFPA is of significance to effects of surgery and patients’prognosis.Patients’age,tumor volume,suprasellar growth tendency and visual impairment were highly correlated with the invasiveness of NFPA(P<0.05).The analysis of Kaplan-Meier methods of patients’recurrence-free survival showed that invasive NFPA patients has a shorter asymptomatic survival time than non-invasive NFPA patients(P=0.020<0.05).RNF41 expression in non-invasive NFPA patients was greatly stronger in invasive NFPA patients(P=0.003<0.05).RNF41 expression is highly correlated with tumor volume,invasiveness and tumor recurrence(P<0.05).The analysis of Kaplan-Meier methods of patients’recurrence-free survival showed that patients who showed stronger RNF41expression has a longer asymptomatic survival time than those who showed weaker RNF41 expression(P=0.016<0.05).Chi-q analysis and multivariate COX regression analysis showed that RNF41 expression was an independent predictor of recurrence-free survival.2.The analysis of 40 collected showed that the number of MDM2 high expression cases in invasive group and non-invasive group is 15 and 9,which showed significant difference in two group(X~2=5.013,P=0.025<0.05)s.The number of P53 high expression in two groups was 16 and 9,which showed greatly difference(X~2=5.227,P=0.022<0.05),too.The expression of RNF41 was negatively correlated to MDM2(r=﹣0.452,P=0.003<0.01)and P53(r=﹣0.422,P=0.007<0.01).MDM2 and P53expression showed positively correlation(r=0.525,P=0.001<0.01),which HER2 and HER3 showed(r=0.424,P=0.006<0.01),too.There are no difference found from HER2and HER3 expression between the two groups(P>0.05).And expression of HER2 and HER3 didn’t show significant correlation with other proteins(P>0.05).Conclusion:1.RNF41 expression is significantly lower in invasive NFPA,and RNF41 is an independent prognostic factor for recurrence free progression of NFPA.2.MDM2 and P53 were significantly overexpressed in invasive NFPA,whileHER2 and HER3 were not significantly expressed in invasive NFPA.3.RNF41 has an antagonistic relationship with MDM2 and p53 in the invasiveness development mechanism of NFPA,but has nothing to do with HER2 and HER3.