Yun-Song Yang1,2,3, Yi-Xing Ren1,2, Cheng-Lin Liu1,2, Shuang Hao1,2, Xiao-En Xu1,2, Xi Jin4,5, Yi-Zhou Jiang6,7, Zhi-Ming Shao8,9,10. 1. Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. 2. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. 3. Human Phenome Institute, Fudan University, 825 Zhangheng Road, Shanghai, 201203, People's Republic of China. 4. Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. 15111230037@fudan.edu.cn. 5. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. 15111230037@fudan.edu.cn. 6. Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. yizhoujiang@fudan.edu.cn. 7. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. yizhoujiang@fudan.edu.cn. 8. Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. zhimingshao@yahoo.com. 9. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Road, Shanghai, 200032, People's Republic of China. zhimingshao@yahoo.com. 10. Institutes of Biomedical Sciences, Fudan University, 131 Dong-An Road, Shanghai, 200032, People's Republic of China. zhimingshao@yahoo.com.
Abstract
PURPOSE: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. This study aimed to develop a prognostic signature of early-stage TNBC patients to improve risk stratification. METHODS: Using RNA-sequencing data, we analyzed 189 pathologically confirmed pT1-2N0M0 TNBC patients and identified 21 mRNAs that were highly expressed in tumor and related to relapse-free survival. All-subset regression program was used for constructing a 7-mRNA signature in the training set (n = 159); the accuracy and prognostic value were then validated using an independent validation set (n = 158). RESULTS: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs mainly consisted of basal-like immune-suppressed subtype and had higher homologous recombination deficiency scores. We developed a prognostic signature including seven mRNAs (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n = 159) and validation set (n = 158), this signature could identify patients with relatively high recurrence risks and served as an independent prognostic factor. Time-dependent receiver operating curve showed that the signature had better prognostic value than traditional clinicopathological features in both sets. Functionally, we showed that TMEM101 promoted cell proliferation and migration in vitro, which represented a potential therapeutic target. CONCLUSIONS: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. This model may facilitate personalized therapy decision-making for early-stage TNBCs individuals.
PURPOSE: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. This study aimed to develop a prognostic signature of early-stage TNBC patients to improve risk stratification. METHODS: Using RNA-sequencing data, we analyzed 189 pathologically confirmed pT1-2N0M0 TNBC patients and identified 21 mRNAs that were highly expressed in tumor and related to relapse-free survival. All-subset regression program was used for constructing a 7-mRNA signature in the training set (n = 159); the accuracy and prognostic value were then validated using an independent validation set (n = 158). RESULTS: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs mainly consisted of basal-like immune-suppressed subtype and had higher homologous recombination deficiency scores. We developed a prognostic signature including seven mRNAs (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n = 159) and validation set (n = 158), this signature could identify patients with relatively high recurrence risks and served as an independent prognostic factor. Time-dependent receiver operating curve showed that the signature had better prognostic value than traditional clinicopathological features in both sets. Functionally, we showed that TMEM101 promoted cell proliferation and migration in vitro, which represented a potential therapeutic target. CONCLUSIONS: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. This model may facilitate personalized therapy decision-making for early-stage TNBCs individuals.
Authors: A de Nonneville; A Gonçalves; C Zemmour; M Cohen; J M Classe; F Reyal; P E Colombo; E Jouve; S Giard; E Barranger; R Sabatier; F Bertucci; J M Boher; G Houvenaeghel Journal: Eur J Cancer Date: 2017-08-04 Impact factor: 9.162
Authors: Surabhi Amar; Ann E McCullough; Winston Tan; Xochiquetzal J Geiger; Judy C Boughey; Rebecca B McNeil; Kyle E Coppola; Sarah A McLaughlin; Frances M Palmieri; Edith A Perez Journal: Oncologist Date: 2010-10-07
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Authors: Ning Qing Liu; Christoph Stingl; Maxime P Look; Marcel Smid; René B H Braakman; Tommaso De Marchi; Anieta M Sieuwerts; Paul N Span; Fred C G J Sweep; Barbro K Linderholm; Anita Mangia; Angelo Paradiso; Luc Y Dirix; Steven J Van Laere; Theo M Luider; John W M Martens; John A Foekens; Arzu Umar Journal: J Natl Cancer Inst Date: 2014-01-07 Impact factor: 13.506