Transcriptomics-based Analysis Of The Prognostic Role Of MDK Gene In Glioblastoma And The Relationship With Immune Microenvironment

Objective: Glioblastoma(GBM)is one of the most common and lethal primary malignant brain tumors in the human body,and the treatment approach against it is a major challenge in neuro-oncology.Unfortunately,despite years of continuous efforts in basic physiological and clinical research,the prognosis of glioblastoma patients remains poor.Therefore,the search for a new alternative to improve overall survival,progression-free survival and quality of life in glioblastoma patients still requires further exploration.MDK is a protein that initiates signaling through a ligand-dependent receptor-activated biological response that is upregulated in multiple cancer types,and downstream signaling may be associated with a large number of phenotypic features that contribute to cancer development and progression.However,the clinical value of MDK in glioblastoma(GBM)in relation to the tumor immune microenvironment is unclear.The aim of this study was to investigate its clinical prognostic value in GBM and its relationship with the tumor immune microenvironment.Methods: We used UCSC XENA(http://xenabrowser.net/datapages)RNAseq data in TPM format of TCGA-GBM and GTEx processed uniformly by the Toil process to obtain 166 GBM tissues and 1157 normal tissues,using t and chi-square tests to assess MDK expression levels and their clinical significance in GBM.And the prognostic value of MDK in GBM was determined by Kaplan-Meier method and Cox regression analysis.Gene set enrichment analysis(GSEA)was used to screen biological pathways and Spearman correlation analysis to determine the association between MDK expression and immune cell infiltration,immune checkpoint genes and TP53.Analysis of MDK expression transfer between different subtypes of GBM by single cell RNA sequencing.Results: MDK was highly expressed in GBM patients and had a high diagnostic value with an AUC of 0.984.Kaplan-Meier survival and Cox regression analyses showed that high MDK expression was associated with poor prognosis in GBM patients.Gene set enrichment analysis(GSEA)revealed that high expression of MDK was significantly correlated with mitotic cell cycle,DNA repair,Rho GTPase signaling,TP53 transcriptional regulation,and cytokinesis checkpoint pathway.We also explored the correlation between MDK and tumor immune interactions and found that MDK expression levels significantly correlated with immune cell infiltration,immune checkpoint genes,and TP53 in GBM.Conclusion: MDK is a pan-cancer biomarker expressed in a wide range of cancerous tissues that can be used as a predictive biomarker of a patient’s likelihood of responding to treatment or developing toxicity and allows monitoring of their treatment outcome.MDK is a potential target for improving the efficacy of immunotherapy in patients with GBM.Thus,MDK as a secreted protein could serve as a routinely available blood or urine biomarker that may play an effective role in predicting immunotherapeutic response.