Bioinformatics Analysis Of Human Glioma Based On TCGA Database And Expression Of KNL1 In Human Glioma And Its Clinical Significance

BackgroundGlioma is the most common primary malignant tumor in the brain,accounting for about 60% of all intracranial tumors.The incidence is high and the prognosis is extremely poor.The median survival time of patients is only about 15 months.According to the degree of benign and malignant,the WHO classifies gliomas into grades ?-?,of which grades ? and ? are malignant gliomas,accounting for about 78% of all gliomas.At present,the clinical treatment of gliomas mainly uses surgical resection + postoperative radiotherapy and chemotherapy,but the treatment effect is still not ideal,the prognosis is extremely poor,and the quality of life of patients is seriously affected.Glioma is closely related to genetic changes in the brain,involving multi-stage and multi-step processes involving multiple genes,but its specific mechanism has not yet been elucidated.At present,it has been confirmed that the expression of kinetochore scaffold 1,KNL1 is associated with the occurrence of various cancers such as primary lung cancer,rectal cancer,and breast cancer,and its pathological differentiation,proliferation,apoptosis,and prognosis.Therefore,KNL1 may be used as a potential tumor therapy target and provide a new theoretical basis for the treatment of tumors.However,whether KNL1 can play a role in gliomas remains unclear.ObjectiveThis study aimed to clarify the expression and molecular mechanism of KNL1 in gliomas,to explore the potential of KNL1 as a potential therapeutic target for gliomas,and its clinical application value,provide a new theoretical basis for the treatment of gliomas.MethodsThe RNA-seq data and clinical data of glioma and normal control were downloaded from TCGA database and GEPIA database.The expressions of KNL1 in different grades of glioma were analyzed.Suvival analysis was performed to explore the prognosis value of KNL1.Then,the genes that were co-expressed with KNL1 were screened,followed by differentially expression analysis and functional enrichment analysis.Finally the dataset in CGGA database was used to validate the expression of KNL1.A total of 120 glioma patients and 20 controls were selected from January 2015 to February 2017 in the Department of Neurosurgery of the First Affiliated Hospital of Zhengzhou University.Immunohistochemistry(IHC)was used to detect the expression of KNL1 in glioma tissue and normal brain tissue samples.The correlations between KNL1 expression and clinicopathological factors were annlyzed using Spearman correlation analysis.Kaplan-Meier analysis was used to investigate the effect of KNL1 expression on overall survival(OS)and progression free survival(PFS)of patients.Univariate and multivariate Cox regression analysis were performed to assess the factors related to OS and PFS of patients.Results1.The results of TCGA data show that the expression level of KNL1 is different from that of different stages of gliomas,that is,the expression level of KNL1 is compared between Grade II and Grade ?,Grade ? and Grade IV,and Grade II and Grade IV.Significant difference(P<0.05).2.The results of KNL1 gene-related survival analysis showed that high and low expression of KNL1 had a significant difference in overall survival,and the high expression group was associated with a poorer prognosis(P<0.05).3.The results of gene regulation network analysis show that there are 50 genes closely related to the regulation of KNL1 family,including three roles(INS,CREB1,PITX2 and other genes can regulate the expression of KNL1 gene;CDK1,CDC42,CCNB1 can regulate KNL1 State change;AURKB can regulate KNL1 phosphorylation).4.The results of gene co-expression analysis in the regulatory network show that there are 18 genes co-expressed with KNL1(ZWINT,PLK1,NDC80,MAD2L1,KNTC1,KIF2 C,ESPL1,CENPF,CENPE,CENPA,CDK1,CDC20,CCNB2,CCNB1,BUB1 B,BUB1,BIRC5,AURK8),and all have a positive correlation with the expression of KNL1(P<0.05).5.Co-expression differential gene analysis results showed that: the expression levels of KNL1 co-expressed genes in GBM group and control group and LGG group and control group were compared by T test.There were 17 genes(KNL1,ZWINT,PLK1,NDC80,MAD2L1,KIF2 C,ESPL1,CENPF,CENPA,CDK1,CDC20,CCNB2,CCNB1,BUB1 B,BUB1,BIRC5,AURK8)have significant differences in at least one set of comparisons(P<0.05),of which KNL1 is in GBM Differential expression in the group(P<0.05),but not in the LGG group(P>0.05).6.Enrichment analysis results show that: according to the differential genes related to KNL1,find potential signal pathways(GO BP)involved in the development of glioma disease,including: Chromosome segregation,Mitotic sister chromatic segregation,etc.7.CGGA verification analysis results show that: KNL1 expression is different in glioma samples of different grades in the CGGA database(P<0.05),which is consistent with the results of previous analysis.8.Immunohistochemical staining results showed that compared with the control group,KNL1 was highly expressed in gliomas,and the difference was statistically significant(P<0.05).The positive expression of KNL1 in grade ? glioma and grade ? glioma was higher than that in the control group,the difference was statistically significant(P<0.05).9.The analysis results of KNL1 expression and clinical pathological data of glioma patients show that: in gliomas,the positive and negative expressions of KNL1 are at age(?50 years old and >50 years old),pathological grade(grade II,grade ?,grade ?)Grade),KPS score(?70 points and <70 points),the difference was statistically significant(P<0.05).Spearmen rank analysis showed that KNL1 positive expression was positively correlated with Ki-67(P<0.05).10.The analysis of the relationship between the expression of KNL1 and the prognosis of glioma patients showed that: Kamplan-Meier survival analysis showed that compared with patients with negative KNL1 expression,patients with positive KNL1 expression had shorter PFS and OS,and the difference was statistically significant(P< 0.05).11.The results of COX regression analysis of PFS and OS affecting glioma patients showed that KNL1 expression,KPS score,and WHO classification were independent prognostic factors affecting OS and PFS of gliomas(P <0.05).Conclusion1.The expression of KNL1 in glioma patients increases,and it is positively correlated with the malignancy and prognosis of the tumor,and can be used as an indicator to judge the clinical prognosis.2.The abnormal expression of KNL1 and its co-expressed genes in gliomas may play a role in the pathogenesis of gliomas through functions such as chromosome separation and cell cycle.