PMID- 34536743 OWN - NLM STAT- MEDLINE DCOM- 20220221 LR - 20220221 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 100 DP - 2021 Nov TI - Identification of a novel immune-related prognostic signature associated with tumor microenvironment for breast cancer. PG - 108122 LID - S1567-5769(21)00758-X [pii] LID - 10.1016/j.intimp.2021.108122 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Ding, Shuning AU - Ding S AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Sun, Xi AU - Sun X AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Zhu, Li AU - Zhu L AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Li, Yafen AU - Li Y AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Chen, Weiguo AU - Chen W AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Shen, Kunwei AU - Shen K AD - Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: kwshen@medmail.com.cn. LA - eng PT - Journal Article DEP - 20210915 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Biomarkers, Tumor) SB - IM MH - Biomarkers, Tumor MH - Breast Neoplasms/*diagnosis/*genetics/immunology MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Prognosis MH - Transcriptome MH - Tumor Microenvironment/*genetics/*immunology OTO - NOTNLM OT - Breast cancer OT - Gene signature OT - Immune system OT - Prognosis OT - Survival EDAT- 2021/09/19 06:00 MHDA- 2022/02/22 06:00 CRDT- 2021/09/18 20:20 PHST- 2021/03/22 00:00 [received] PHST- 2021/08/29 00:00 [revised] PHST- 2021/08/31 00:00 [accepted] PHST- 2021/09/19 06:00 [pubmed] PHST- 2022/02/22 06:00 [medline] PHST- 2021/09/18 20:20 [entrez] AID - S1567-5769(21)00758-X [pii] AID - 10.1016/j.intimp.2021.108122 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Nov;100:108122. doi: 10.1016/j.intimp.2021.108122. Epub 2021 Sep 15.