Establishment and clinical application of a prognostic gene model for Luminal B subtype breast cancer
Objective Based on the highly different prognosis of Luminal B breast cancer,a prognostic risk scoring model was established to guide and predict the prognosis and survival of patients with Luminal B breast cancer.Methods Total-ly 194 cases of Luminal B breast cancer and 119 cases of normal breast tissue adjacent to cancer were selected from the da-tabase for differential gene expression analysis from the cancer genome atlas(TCGA).Combined with bioinformatics methods,the genome related to prognosis was obtained through differential gene expression analysis.The prognosis mod-el was constructed by least absolute shrinkage and selection operator(LASSO)to conduct Cox regression analysis;that was,a risk model related to prognosis and constructed for the differential expression of the genome in normal breast tissue and breast cancer tissue,and the clinical application of the model was verified.Simultaneously we explored the molecular mechanisms that may trigger this risk model.Immunohistochemical method was used to detect the expression of related genes in 64 triple positive breast cancer tissues from January 1,2015 to December 31,2022 in the Breast Center of Nan-chang People's Hospital.Results LASSO Cox regression analysis was used to construct the prognosis model,when 11 genes were included,the risk efficiency was the highest.The data set verified that its 95％confidence interval had signifi-cant statistical differences.The area under the ROC curve for 1,3,and 5 years was 0.975,0.829,and 0.885,respec-tively.The prognosis of the high-risk group was poor,and the difference was statistically significant,all P＜0.05.The results of univariate Cox regression analysis showed a correlation between risk score and prognosis,with HR=5.72,95％CI ranging from 3.34 to 9.81,P＜0.001.The results of multivariate Cox regression analysis showed that risk score(HR=8.91,95％CI:4.23-18.72,P＜0.001)and age(HR=1.03,95％CI:1.00-1.06,P=0.047)were associated with prognosis.The nomogram intuitively and effectively displayed the impact of different variables on prognosis out-comes,and included factors related to prognosis to construct a nomogramic model.The evaluation of the C-index value of the nomogramic model showed that the C-index value of the model was 0.84,with a 95％CI of 0.75-0.92,P＜0.001.The analysis of enrichment pathways showed that the high-risk group was significantly enriched in pathways such as vari-able splicing and aminoacyl tRNA synthesis,while the low-risk group was enriched in signaling pathways such as cytokine cytokine receptors,primary immunodeficiency,and chemokine receptors.The correlation between tumor microenviron-ment and risk assessment showed that most immune cells scored high in the low-risk group.Immunohistochemical test re-sults showed that ERCC6L,COL11A1,NEURL1,CXCL9,ROPN1,PPP1R16B,PIGR were positive in triple positive breast cancer tissue samples,and TLCD1,ABCA10,TMEM273,ARHGAP40 were weakly positive.Conclusion The risk model score constructed can provide clinicians with a quantitative method to predict the prognosis,and can be used as a biomarker for the prognosis of Luminal B breast cancer patients.
breast cancerLuminal B subtypemolecular classificationprognosis model
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