| Objective To evaluate the prognostic value and differential diagnosis of CMTM3 in glioma,and to analyze its feasibility and correlation as a potential immunotherapy target.Methods Transcriptome sequencing data from LGG（WHO grade II and WHO grade III）and other tumor patients were downloaded from cancer Genome Atlas（TCGA）database,and brain tissue sequencing data from normal patients were downloaded from GTEX database.CMTM3 expression was compared between LGG（WHO grade II and WHO grade III）and normal brain tissue.Using the GEPIA database,CMTM3 expression was significantly elevated in LGG（WHO grade II and WHO grade III）compared to normal brain tissue.Combined with clinical and sequencing data of LGG（WHO grade II and WHO grade III）patients in TCGA,the expression of CMTM3 in each subgroup was analyzed for statistical significance.Univariate and multivariate COX regression analysis demonstrated whether CMTM3 was an independent risk factor for LGG（WHO grade II and WHO grade III）.The survival curves of CMTM3 in LGG（WHO grade II and WHO grade III）as a whole and subgroups were plotted to compare the overall survival（OS）between the high and low expression groups.Time-dependent ROC curves were used to predict survival outcomes in patients with LGG（WHO Grade II and WHO Grade III）.The diagnostic value of CMTM3 was evaluated by ROC curve.Gene set enrichment analysis（GSEA）looked for CMTM3 signaling pathways that might be involved in the progression of LGG（WHO Grade II and WHO Grade III）.The possible miRNA of CMTM3 was regulated by Starbase database prediction.The TIMER database is used to analyze immune infiltration.The survival probability of LGG（WHO Grade II and WHO Grade III）patients at different time was predicted by a lipopograph model.Results CMTM3 is highly expressed in most tumors.CMTM3 expression was significantly elevated in LGG（WHO grade II and WHO grade III）compared with normal brain tissue.The expression of CMTM3 in LGG subgroups（WHO grade II and WHO grade III）was statistically different.The expression of CMTM3 in WHO grade III gliomas was significantly higher than that in WHO grade II gliomas.CMTM3 expression of IDH wild-type LGG（WHO grade II and WHO grade III）was significantly higher than that of IDH mutants.CMTM3 expression in patients with 1P/19 q combined deletion was significantly lower than that in patients without deletion.CMTM3 expression was also significantly different between the subgroup aged less than 40 years and the subgroup aged more than 40 years.Univariate and multivariate COX regression models showed that CMTM3 expression was an independent risk factor for LGG（WHO grade II and WHO grade III）.The survival curve showed that the overall survival（OS）of the low expression group was significantly longer than that of the high expression group in the whole LGG.LGG（WHO grade II and WHO grade III）is divided into subgroups.In the WHO grade III subgroup,the overall survival（OS）was shorter in the group with high CMTM3 expression.In the IDH wild-type subgroup,the overall survival（OS）of CMTM3 with high expression was significantly lower than that of the low expression group.High expression of CMTM3 also indicated a shorter overall survival（OS）in the subgroup without 1p/19 q deletion and older than 40 years.The time-dependent ROC curve was used to predict patient survival outcomes,and the AUC for predicting 1-year and 3-year survival outcomes in LGG（WHO grade II and WHO grade III）patients was 0.821 and 0.750,respectively.The performance of CMTM3 in differentiating LGG from normal brain tissue was evaluated by ROC curve.The area under ROC curve（AUC）,specificity and sensitivity were 0.990,96.2%,96.4%and 3.935 respectively.CMTM3 differentiated LGG（WHO grade II and WHO grade III）from GBM with an AUC of 0.847,specificity of 73.0%,sensitivity of 87.5%,and optimal threshold of 6.035.The AUC of CMTM3 for differentiating WHO Grade III glioma from WHO grade IV glioma was 0.783,the sensitivity was 85.7%,the specificity was 62.1%,and the optimal threshold was 6.053.CMTM3 also has certain diagnostic value in differentiating IDH from mutant or wild type,with AUC of 0.762,sensitivity of 70.8%,specificity of 78.4%,and optimal threshold of 4.090.Gene set enrichment analysis showed that CMTM3 was significantly enriched in four pathways.Combined with the joint prediction of multiple databases,it was found that the most likely miRNA regulating CMTM3 was hsa-miR-149-5p.CMTM3 has a high correlation with a variety of immune cells in LGG.Conclusion CMTM3 is an independent prognostic factor for LGG（WHO grade II and WHO grade III）and can be used as a new prognostic marker for LGG（WHO grade II and WHO grade III）.CMTM3 has high diagnostic value and can assist in the clinical differential diagnosis of LGG and normal tissue,LGG and GBM,WHO grade III and WHO Grade IV,and IDH wild-type or mutant.CMTM3 is expected to be a potential immunotherapy target for LGG（WHO grade II and WHO grade III）. |
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