Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA exp...Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.展开更多
Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltra...Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltration of TUBA1C in breast cancer patients.Methods:The expression of TUBA1C as well as its associations with clinical traits and prognosis were examined using the Cancer Genome Atlas,DepMap and Human Protein Atlas databases.The primary pathway involved in breast cancer based on TUBA1C was examined using gene set enrichment analysis software,CancerSEA and the GSCALite database.Then,using ssGSEA and Spearman methods,the interaction between TUBA1C and immune cell infiltration was examined.The R package“pRRophetic”investigated the sensitivity of TUBA1C to chemotherapy and targeted treatment drugs.Results:Patients with BC had significantly higher levels of TUBA1C expression.The poor prognosis of breast cancer patients was linked to the increased expression of TUBA1C.The expression of TUBA1C was identified as an independent risk factor for breast cancer by univariate and multivariate Cox regression analysis.An examination of the gene set enrichment analysis and CanerSEA databases revealed that TUBA1C primarily engages in the cell cycle and DNA replication pathways to have a carcinogenic effect.Th2 cells,aDC,Th1 cells,macrophages,NK CD56dim,neutrophils,DC,Treg,pDC,CD8 T cells,mast cells,NK cells and eosinophils were the 13 types of tumor immune infiltrating cells that TUBA1C was associated with by ssGSEA.Additionally,we discovered that TUBA1C was closely associated with a number of chemotherapy and targeted therapy medications.Our findings suggest that TUBA1C is a novel prognostic predictor of breast cancer,related to immune infiltration and drug sensitivity,and may serve as a new target for breast cancer treatment in the future.Conclusion:According to our study,TUBA1C exerts a carcinogenic effect in breast cancer through oncogenic pathway such as the cell cycle and is associated with immune cell infiltration and predicts response to chemotherapy and targeted therapy.展开更多
目的探讨乳腺癌扩增基因1(amplified in breast cancer 1,AIB1)在肺腺癌中的表达及其与患者预后的关系,探讨AIB1促进肺腺癌细胞生长转移的机制。方法收集2015年1月1日至2018年12月31日首都医科大学宣武医院收治的肺腺癌患者102例。通过...目的探讨乳腺癌扩增基因1(amplified in breast cancer 1,AIB1)在肺腺癌中的表达及其与患者预后的关系,探讨AIB1促进肺腺癌细胞生长转移的机制。方法收集2015年1月1日至2018年12月31日首都医科大学宣武医院收治的肺腺癌患者102例。通过免疫组化检测肺腺癌组织中AIB1的表达,分析AIB1表达与患者预后相关性。通过质粒转染使肺腺癌细胞株A549过表达AIB1,观察AIB1过表达对细胞生长、细胞周期及划痕愈合能力的影响。结果102例患者中,AIB1高表达者60例,低表达者42例,死亡患者AIB1的表达显著高于存活患者(P=0.001),AIB1高表达者累计生存率显著降低(P<0.001)。与转染空质粒相比,转染AIB1的A549细胞生长增快,细胞周期进程加速,划痕愈合能力增强(P<0.05)。结论AIB1可以促进肺腺癌细胞生长、增殖和转移,并与肺腺癌患者的不良预后相关。展开更多
文摘Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.
基金supported and funded by the Tai'an Science and Technology Development Plan(Guiding Plan)(No.2018NS0222).
文摘Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltration of TUBA1C in breast cancer patients.Methods:The expression of TUBA1C as well as its associations with clinical traits and prognosis were examined using the Cancer Genome Atlas,DepMap and Human Protein Atlas databases.The primary pathway involved in breast cancer based on TUBA1C was examined using gene set enrichment analysis software,CancerSEA and the GSCALite database.Then,using ssGSEA and Spearman methods,the interaction between TUBA1C and immune cell infiltration was examined.The R package“pRRophetic”investigated the sensitivity of TUBA1C to chemotherapy and targeted treatment drugs.Results:Patients with BC had significantly higher levels of TUBA1C expression.The poor prognosis of breast cancer patients was linked to the increased expression of TUBA1C.The expression of TUBA1C was identified as an independent risk factor for breast cancer by univariate and multivariate Cox regression analysis.An examination of the gene set enrichment analysis and CanerSEA databases revealed that TUBA1C primarily engages in the cell cycle and DNA replication pathways to have a carcinogenic effect.Th2 cells,aDC,Th1 cells,macrophages,NK CD56dim,neutrophils,DC,Treg,pDC,CD8 T cells,mast cells,NK cells and eosinophils were the 13 types of tumor immune infiltrating cells that TUBA1C was associated with by ssGSEA.Additionally,we discovered that TUBA1C was closely associated with a number of chemotherapy and targeted therapy medications.Our findings suggest that TUBA1C is a novel prognostic predictor of breast cancer,related to immune infiltration and drug sensitivity,and may serve as a new target for breast cancer treatment in the future.Conclusion:According to our study,TUBA1C exerts a carcinogenic effect in breast cancer through oncogenic pathway such as the cell cycle and is associated with immune cell infiltration and predicts response to chemotherapy and targeted therapy.
文摘目的探讨乳腺癌扩增基因1(amplified in breast cancer 1,AIB1)在肺腺癌中的表达及其与患者预后的关系,探讨AIB1促进肺腺癌细胞生长转移的机制。方法收集2015年1月1日至2018年12月31日首都医科大学宣武医院收治的肺腺癌患者102例。通过免疫组化检测肺腺癌组织中AIB1的表达,分析AIB1表达与患者预后相关性。通过质粒转染使肺腺癌细胞株A549过表达AIB1,观察AIB1过表达对细胞生长、细胞周期及划痕愈合能力的影响。结果102例患者中,AIB1高表达者60例,低表达者42例,死亡患者AIB1的表达显著高于存活患者(P=0.001),AIB1高表达者累计生存率显著降低(P<0.001)。与转染空质粒相比,转染AIB1的A549细胞生长增快,细胞周期进程加速,划痕愈合能力增强(P<0.05)。结论AIB1可以促进肺腺癌细胞生长、增殖和转移,并与肺腺癌患者的不良预后相关。
