Research On The Molecular Mechanism Of Tumorigenesis Of Nonfunctioning Pituitary Adenoma By The High Throughput Sequencing

Objective To investigate the differential expressions of RNAs and proteins in nonfunctional pituitary adenomas by transcriptome and proteomics sequencing techniques in order to discover new valuable molecular markers of nonfunctional pituitary adenomas and explore the tumorigenesis of them via the biological analysis.Methods Through the transcriptomics sequencing,we established the RNA expression profile of nonfunctional pituitary adenomas by the process of total RNA extraction,cDNA library establishment,high-throughput sequencing and differential expression gene analysis.Differentially expressed proteins were identified by proteomics analysis of isotope labeling relative and absolute quantification techniques.The proteins were analyzed in terms of molecular function,cell location and biological processes for finding the key protein molecules which are related to the development of tumors.Results By the transcriptomics sequencing,2137 differential expressed genes were identified.Through the function analysis,MAPK signaling pathway,proteoglycans in cancer,Rap1 signaling pathway,Focal adhesion,Oxytocin signaling pathway,cGMP-PKG signaling pathway,and Inflammatory mediator regulation of TRP channels are enriched in KEGG analysis.These pathways provides a new vision for us to explore the molecular mechanism of tumorigenesis of nonfunctional pituitary adenomas.We used ClueGO software to draw a picture of the KEGG pathway network,and obtained four key genes named MAPK3,PRKCA,PIK3CD and SRC.The MAPK3-encoded protein is a member of the MAP kinase family,which expresses in all mammalian tissues and acts as a key regulator of cell proliferation and differentiation.Therefore,as an important gene affecting tumor proliferation and differentiation,whether it plays the same role in pituitary adenomas is worthy for a further study.Compared with the control group,we found 50 types of up-regulated proteins and 101 down-regulated ones in the serum of nonfunctional pituitary adenomas.Gene ontology analysis showed that most differentially expressed proteins were in the extracellular region.Pathway enrichment analysis showed that most proteins involved in the complement and coagulation cascade pathway.Conclusions Proteins related to the complement system is significantly up-regulated in the serum of the pituitary adenomas,which may enhance the body immune response to tumor cells by activating the classical pathway of complement.TGF? is down-regulated in tumor serum.A previous study suggested that the inhibition of TGF? pathway may be closely related to the occurrence and invasion of nonfunctional pituitary adenoma.Our study also explored some biomarkers which could serve as potential predict and diagnose molecular in nonfunctional pituitary adenoma.