IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Correlations between P2RX1 Expression and Gastrointestinal Cancers Prognosis and Immune Infiltration Based on Bioinformatics Analysis

This study was conducted to explore the correlations between the expression,methylation,and various clinicopathological factors of purinergic P2X1 receptor(P2RX1)and the prognosis of patients with gastrointestinal tumors.The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of P2RX1 in different types of gastrointestinal cancers.Kaplan-Meier analysis and univariate Cox regression analysis were used to analyze the correlations between P2RX1 expression and the prognosis of various gastrointestinal tumors.Correlations between P2RX1 expression and N6 methyladenine(m6A)-related genes as well as immune checkpoint genes were analyzed by R packages(R version:4.0.3)based on TCGA database.The association between P2RX1 methylation level and the prognosis of patients with gastrointestinal cancers was analyzed using the MethSurv database.In order to explore the biological functions of P2RX1 in hepatocellular carcinoma,the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis were carried out using R software.In order to evaluate the correlations between P2RX1 and tumor immune infiltration,Spearman correlation test was performed.The correlations between P2RX1 expression and immune score as well as immune checkpoint genes were analyzed based on TCGA and Tumor Immune Estimation Resource(TIMER)databases.The expression of P2RX1 was found to be significantly downregulated in gastrointestinal tumors except in cholangiocarcinoma(P<0.05).High expression of P2RX1 tended to present better prognosis in hepatocellular carcinoma(P<0.05).It was noted that cg06475633 of P2RX1 presented a higher methylation level compared with other CpG sites in hepatocellular carcinoma.Overall,six CpGs of P2RX1 were associated with significant prognosis in patients with hepatocellular carcinoma(P<0.05).Among all the 20 m6A-related genes,Wilms'tumor 1-associating protein(WTAP)was the most strongly correlated with P2RX1 in hepatocellular carcinoma.Gene enrichment analysis showed that P2RX1 is widely involved in the proliferation,activation,organization,and differentiation of various immune cells.After investigating the TIMER database,P2RX1 was found to be tightly correlated with immune infiltrating cells in gastrointestinal tumors,especially with dendritic cells.Moreover,P2RX1 was found to be strongly positively associated with programmed cell death 1(PD1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA4)in hepatocellular carcinoma(P<0.05).In conclusion,the dual role of P2RX1 in cancers and its involvement in the recruitment as well as regulation of tumor infiltrating cells in gastrointestinal cancers may be appreciated through this study.

Development of a prognostic signature for esophageal cancer based on a novel 7-DNA damage repair genes signature

Esophageal cancer(EC)was an aggressive malignant neoplasm characterized by high morbidity and poor prognosis.Identifying the changes in DNA damage repair genes helps to better understand the mechanisms of carcinoma progression.In this study,by comparing EC samples and normal samples,we found a total of 132 DDR expression with a significant difference.Moreover,we revealed higher expression of POLN,PALB2,ATM,PER1,TOP3B and lower expression of HMGB1,UBE2B were correlated to longer OS in EC.In addition,a prognostic risk score based on 7 DDR gene expression(POLN,HMGB1,TOP3B,PER1,UBE2B,ATM,PALB2)was constructed for the prognosis of EC.Meanwhile,EC cancer samples were divided into 3 subtypes based on 132 DDR genes expressions.Clinical profile analysis showed cluster C1 and C2 showed a similar frequency of T2,which was remarked higher than that in cluster 3.Moreover,we found the immune cell inflation levels were significantly changed in different subtypes of EC.The infiltration levels of T cell CD8+,B cell and NK cells were greatly higher in cluster 2 than that in cluster 1 and cluster 3.The results showed T cell CD4+infiltration levels were dramatically higher in cluster 1 than that in cluster 2 and cluster 3.Finally,we perform bioinformatics analysis of DEGs among 3 subtypes of EC and found DDR genes may be related to multiple signaling,such as Base excision repair,Cell cycle,Hedgehog signaling pathway,and Glycolysis/Gluconeogenesis.These results showed DDR genes may serve as new target for the prognosis of EC and prediction of the potential response of immune therapy in EC.