The Target E2F Family Gene PTTG1 for Prediction of Distant Relapse-Free Survival in Breast Cancer Patients Receiving Taxane and Anthracycline-Based NACT

Abstract

Background: The breast cancer is the most commonly diagnosed cancer in recent years. The use of neoadjuvant chemotherapy (NACT) makes a significant contribution to chemotherapy in breast cancer. We aimed to develop the novel model as a predictor of distant relapse-free survival (DRFS) in breast cancer patients receiving taxane and anthracycline-based NACT.Methods: We collected the mRNA expression datasets of patients from GSE25055 and GSE25065 in Gene Expression Omnibus (GEO). Univariate and Multivariate Cox Regression Analyses were conducted to achieve the prognostic genes that associated with DRFS. Moreover, the E2F target genes were obtained from GSEA. We obtained the intersection genes between the prognostic genes and E2F target genes, then validated in GSE32603 dataset. And we established a nomogram model based on PTTG1 expression level and several clinical characteristics.Results: There were 95 genes confirmed to be associated with DRFS both in GSE25055 and GSE25065. And PTTG1 was validated as a gene related to DRFS and associated with E2F target hallmark using GSEA analysis and chosen as our target gene. The AUC of PTTG1 model was 0.682 indicating a relatively poor prediction performance. Then a novel nomogram was conducted, the receiver operating characteristic (AUC=0.849), C-index (0.805) and calibration plots were applied to assess the effect of this model.Conclusion: Our study found that the E2F target genes, such as the PTTG1 may serve as a potential biomarker in breast cancer, and provided superior estimation of DRFS, which can guide the clinical practice in NACT of breast cancer.