A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer.
Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong
Author Information
Chang Min Kim: CbsBioscience. Inc., Daejeon, Korea.
Kyong Hwa Park: Division of Medical Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Yun Suk Yu: CbsBioscience. Inc., Daejeon, Korea.
Ju Won Kim: Division of Medical Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Jin Young Park: CbsBioscience. Inc., Daejeon, Korea.
Kyunghee Park: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Jong-Han Yu: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jeong Eon Lee: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sung Hoon Sim: Breast Cancer Center, National Cancer Center, Goyang, Korea.
Bo Kyoung Seo: Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
Jin Kyeoung Kim: Department of Pharmacy, College of Pharmacy, CHA University, Seongnam, Korea.
Eun Sook Lee: Breast Cancer Center, National Cancer Center, Goyang, Korea.
Yeon Hee Park: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sun-Young Kong: Targeted Therapy Branch, Research Institute, National Cancer Center, Goyang, Korea.
PURPOSE: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. MATERIALS AND METHODS: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. RESULTS: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. CONCLUSION: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
