Study On Biomarkers And Mechanisms Of Inflammatory Myofibroblastic Tumor

Inflammatory myofibroblastic tumor(IMT)is a medically rare solid tumor with a low degree of malignancy.With the development of bioinformatics and the derivation of "precision medicine",the individualized treatment of IMT has received more and more attention.However,there is currently no clear diagnostic biomarker for IMT other than ALK,and the molecular mechanism of action is unclear.Therefore,this paper aims to explore the pathways and potential biomarkers of IMT through the molecular level of the mechanism and provide clinical materials for the rare disease.This research is divided into two parts:experiment and data analysis.First,using self-controlled research strategies,high-throughput sequencing was performed between the tumor tissue and peripheral blood of the IMT patient.Somatic mutation genes were obtained by the comparative analysis of the data and applied for functional analysis and Multi-Dendrix algorithm analysis.The IMT patient also suffereda diabetic nephropathy(DN),so the second part of the experiment used peripheral blood transcriptome sequencing analysis of the IMT patient and 5 DN patients of the similar age and same gender(control group)to obtain differentially expressed genes.GO terms,KEGG pathway enrichmentanalysis and MCODE algorithm analysis were used for the differentially expressed genes.At the same time,hierarchical clustering analysis,gene overlap analysis,and protein interaction analysis were performed by combining somatic mutation genes with differentially expressed genes in peripheral blood.Through the above analysis,we obtained 94 somatic mutation genes and 559 peripheral blood differentially expressed genes.Differentially expressed genes in peripheral blood are significantly associated with Yersinia infection,ErbB signaling pathway and other pathways.Somatic mutation genes are significantly related to herpes simplex infection and proteoglycan in cancer.Multi-Dendrix algorithm analysis determined the two main driving pathways of the IMT:KLRB1-ERBB2 and ZCCHC14-LRRC41.It was found that the KLRB1 gene is at the node position of immune-related pathways and cancer-related pathways,which may be a pathogenic gene in IMT.Gene overlap analysis and MCODE analysis showed that there are associations between somatic mutant genes and differentially expressed genes in gene name,gene function and protein interaction.This article is the first attempt to apply peripheral blood transcriptome to the analysis of IMT.Integrating genomics and transcriptomics data,it was found for the first time that the ERBB2 gene and ErbB pathway played an important role in IMT.In addition,the study found that infection-related pathways were closely related to IMT.These findings help to understand the mechanism of IMT and provide powerful theoretical materials for clinical diagnosis and treatment.It actively promotes the construction of domestic rare disease databases.