Prognostic Role of KRAS mRNA Expression in Breast Cancer

Ki-Tae Hwang; Byoung Hyuck Kim; Sohee Oh; So Yeon Park; Jiwoong Jung; Jongjin Kim; In Sil Choi; Sook Young Jeon; Woo-Young Kim

doi:10.4048/jbc.2019.22.e55

Prognostic Role of KRAS mRNA Expression in Breast Cancer

J Breast Cancer. 2019 Dec;22(4):548-561. doi: 10.4048/jbc.2019.22.e55.

Authors

Ki-Tae Hwang¹, Byoung Hyuck Kim², Sohee Oh³, So Yeon Park⁴, Jiwoong Jung⁵, Jongjin Kim¹, In Sil Choi⁶, Sook Young Jeon⁷, Woo-Young Kim⁸

Affiliations

¹ Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
² Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
³ Department of Biostatistics, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
⁴ Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
⁵ Department of Surgery, Seoul Medical Center, Seoul, Korea.
⁶ Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
⁷ Department of Surgery, Graduate School, Kyung Hee University, Seoul, Korea.
⁸ College of Pharmacy, Sookmyung Women's University, Seoul, Korea.

Abstract

Purpose: We investigated the prognostic role of KRAS mRNA expression in breast cancer using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases.

Methods: Clinical and biological data of 1,093 breast cancers from TCGA database and 1,904 breast cancers from METABRIC database were analyzed. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined.

Results: The group with high KRAS mRNA expression showed worse survival than the group with low KRAS mRNA expression regarding both OS (p = 0.012 in TCGA, p < 0.001 in METABRIC) and BCSS (p = 0.001 in METABRIC). According to multivariate analysis, the level of KRAS mRNA expression was an independent prognostic factor in both TCGA (hazard ratio [HR], 1.570; 95% confidence interval [CI], 1.026-2.403; p = 0.038) and METABRIC (HR, 1.254; 95% CI, 1.087-1.446; p = 0.002) databases. The prognostic impact of mRNA expression was effective only for luminal A subtype (p < 0.001 in METABRIC). Positive correlation was observed between mRNA expression and copy number alteration (CNA) (r = 0.577, p < 0.001 in TCGA; ρ = 0.343, p < 0.001 in METABRIC). Methylation showed negative correlations with both mRNA expression and CNA (r = -0.272, p < 0.001 in TCGA). The expression of mRNA had little association with the mutation status in breast cancers, having a mutation frequency of approximately 0.6%.

Conclusion: KRAS mRNA expression was significantly associated with breast cancer prognosis. It was found to be an independent prognostic factor for breast cancer. Prognostic role of KRAS mRNA expression was effective only in luminal A subtype. Further studies are needed to validate the prognostic role of KRAS mRNA expression in breast cancer, thus paving a way for clinical application of KRAS in practice.

Keywords: Breast neoplasms; Prognosis; RNA; ras Proteins.