BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH...BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.展开更多
基金Supported by the Science and Technology Program of Liaoning Province,No.2021-MS-040.
文摘BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.
