Journal Article

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer

Yong Alison Wang, Ben-Long Yu, Tee Benita Kiat Tan, Tzu-Ting Huang, Nicholas Shannon Brian, Skye Hung-Chun Cheng, Chen-Fang Horng, Yu-Hao Cheng, Li-Sun Shih

2017

نظرة عامة

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

• الناشر: Public Library of Science (PLoS),Public Library of Science
• موضوع: Adult / Aged / Biomarkers / Biomarkers, Tumor / BLM gene / Breast cancer / Breast Neoplasms / Breast Neoplasms - genetics / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Breast Neoplasms - therapy / breast surgery / BUB1B gene / C16ORF7 gene / Cancer / cancer grading / cancer prognosis / cancer staging / Cancer therapies / CCNB1 gene / CCR1 gene / chemokine receptor CCR1 / Chemotherapy / classifier / Classifiers / Combined Modality Therapy / DDX39 gene / Developing countries / distant metastasis / DTX2 gene / ENSA gene / external validity / Female / gene / gene classifier / Gene expression / Gene Expression Profiling / genetic algorithm / Health risks / high risk patient / Hospitals / human / human tissue / Humans / internal validity / LDCs / low risk patient / major clinical study / Mammography / Mastectomy / matrix metalloproteinase 15 / Medical prognosis / Medical screening / Medicine / Medicine and Health Sciences / Metastases / Metastasis / Middle Aged / MMP15 gene / Multivariate analysis / Neoplasm Grading / Neoplasm Metastasis / Neoplasm Staging / NFATC2IP gene / OBSL1 gene / Patients / PIM1 gene / probability / Prognosis / Proportional Hazards Models / protein kinase Pim 1 / PTI1 gene / Q / R / Radiation therapy / RCHY1 gene / Regional development / Reproducibility of Results / Research Article / Risk / risk assessment / Risk groups / Science / scoring system / STIL gene / Surgery / TCF3 gene / Tissues / TPX2 gene / transcription factor 7 like 1 / TRPV6 gene / tumor marker / vanilloid receptor 6 / Womens health / Young Adult