Identification of a novel immune-related prognostic signature associated with tumor microenvironment for breast cancer

Background: In the view that immune-related genes play a crucial role in breast cancer progression and long-term patient outcomes, we aimed to identify a novel gene signature based on immune-related genes to improve the prognostic prediction of breast cancer. Methods: RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression analyses were conducted to establish the immune-related prognostic signature (IRPS). Then, the IRPS was validated by Kaplan-Meier analyses, time-dependent ROC curve analyses and multivariate Cox regression analyses. External validation was conducted in GSE96058. Nomogram combining IRPS with clinical factors was developed and then validated by time-dependent ROC curve analyses and calibration plots. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression level of immune-related genes in tumor and normal tissues. Results: The IRPS based on 4 immune-related genes (CCL1, VGF, TSLP, FABP9) were constructed. Patients in the low-risk group had significantly better overall survival than those in the high-risk group (p = 0.0011 in the training set, p = 0.0043 in the validation set, p < 0.0001 in the entire set, p < 0.001 in the external validation set). Multivariate analyses indicated that IRPS could independently predict OS in the training set (HR, 0.48; 95% CI, 0.24-0.83; p = 0.009), validation set (HR, 0.55; 95% CI, 0.34-0.90; p = 0.018), entire set (HR, 0.52; 95% CI, 0.36-0.75; p < 0.001) and external validation set (HR: 0.74, 95% CI: 0.59-0.92, p = 0.007). Sequentially, we establish a nomogram by integrating IRPS and clinical factors, which showed satisfactory predictive performance with 3-year, 5-year, 10-year AUC of 0.701, 0.706 and 0.694. Results of qRT-PCR validated that higher expression level of FABP9, CCL1 and VGF and lower expression level of TSLP in tumor samples compared to normal tissues. Conclusions: Collectively, a four-gene based IRPS was developed and validated for patients with breast cancer. As an independent and robust predictor, the IRPS was constructive to risk stratification of breast cancer.