CD44 Was Expected To Be A Novel Molecule For Evaluation Of Gliomas

Glioma is the most common intracranial malignant tumor.Taking this treatment group as an example,there are more than 200 glioma surgeries every year,of which a considerable number of patients can be diagnosed as glioblastoma in the primary.Although the rest of the patients have undergone surgery,radiotherapy and chemotherapy,or even long-term chemotherapy combined with bevacizumab,the tumor still relapses.Clinical observation shows that the pathological grade of some low-grade gliomas does not change after recurrence.The chance of secondary or even multiple operations makes the survival time longer.However,a considerable number of patients will progress to glioblastoma,with poor prognosis.Which kind of lower grade glioma is more likely to develop into higher grade glioblastoma is often the concern of patients and their families,but there is no clear conclusion at present.In order to study the imaging characteristics of secondary glioblastoma precursor low-grade gliomas,89 patients with recurrent gliomas admitted from October 2011 to October 8,2019 in the First Affiliated Hospital of Zhengzhou University were divided into two groups according to whether they had pathological upgrading after recurrence.It was found that the combined absence of 1p19q was the protective factor of pathological upgrading in the existing clinical pathological molecular markers.After relapse,Ki67 of patients with secondary glioblastoma was higher than that of patients without secondary glioblastoma,but the mutation rates of IDH,ATRX and TP53 were not significantly different between the two groups.In general,under the existing molecular marker system,there was no way to accurately evaluate them The development and prognosis of the disease.Among the 89 patients,19 had complete data of first diagnosis pathology and MRI,5 of them did not progress to glioblastoma after recurrence.Because the enhancement of low-grade gliomas is not clear,it is difficult to determine the extent of tumor and surrounding edema,so we abandon the enhancement sequence and use T2 FLAIR sequence which can better reflect the internal heterogeneity of tumor as the research basis.It was found that the MRI T2 FLAIR images of the patients with low-grade glioblastoma as the precursor of secondary glioblastoma were less homogeneous than those of the patients who did not progress to secondary glioblastoma after recurrence,with rough texture and a large area of equal signal and low signal areas,suggesting that the tumor cells proliferated faster,hypoxia was obvious,and tumor necrosis was more serious.At present,it is known that the formation of pathological blood vessels,the invasion of tumor and the infiltration of immune cells are all related to hypoxia.These pathological processes play a key role in the progress and prognosis of the disease.Therefore,we conclude that compared with the existing molecular markers,the difference of microenvironment in gliomas has a better evaluation effect on the progression and prognosis of the disease.The microenvironment of gliomas consists of tumor cells,immune cells and various factors secreted by them.They interact with each other to jointly regulate and influence the progression of tumors.It is characterized by anti-tumor immunosuppression,which is related to the immune infiltration of tumor related macrophages/microglia,bone marrow-derived suppressor cells(MDSC)and lymphocytes.This study found that the degree of immune infiltration has prognostic value in glioma.The more immune infiltration,the worse prognosis.In addition,tumor microenvironment also plays a role in regulating and supporting CSCs,participating in the resistance of radiotherapy and chemotherapy and tumor recurrence.Therefore,the new molecular markers based on tumor microenvironment can make the diagnosis and prognosis of gliomas,especially low-grade gliomas more accurate.In order to explore new molecular indicators,this study was based on the transcriptome sequencing data and clinical data of low-grade and high-grade gliomas in TCGA and CGGA databases,and used bioinformatics analysis to evaluate the degree of tumor immune invasion.CD44 was obtained by studying the intersection of high and low grade gliomas.At the same time,we used machine learning method to divide glioma into three groups according to the degree of immune infiltration:high,medium and low,and extracted the tag infiltrating cells.In addition,the correlation between the expression of CD44 and the infiltration of glioma and the infiltration of labeled cells was analyzed to verify the good performance of CD44 as a molecular marker.It was confirmed by immunohistochemistry of HPA database that the higher the pathological grade,the higher the expression of CD44.In this study,we found that the microenvironment of glioblastoma is a key factor to evaluate the progression and prognosis of glioblastoma.Antitumor immunosuppression caused by immune cell infiltration is the main feature of glioma microenvironment.Through the study of key molecular markers of tumor immune infiltration microenvironment,it is found that CD44 has a good correlation with the degree of immune infiltration and the amount of infiltration of key cells,and has a prognostic value independent of the existing,molecular markers.HPA database confirmed that the expression of CD44 protein increased with the increase of tumor grade.CD44 has the potential to be a new molecular marker for the progression and prognosis of gliomas,especially low-grade gliomas.Previous studies on CD44 mainly focused on the biological processes of tumor itself,such as increment,invasion,growth and dedifferentiation.This study demonstrated for the first time that CD44 can be used as a marker of tumor immune invasion,focusing on the involvement of CD44 in tumor immune process.