High RRM2 expression has poor prognosis in specific types of breast cancer

• Published in: PloS one Vol. 17; no. 3; p. e0265195
• Main Authors: Shi, Shen-Chao, Zhang, Yi, Wang, Tao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-03-2022; Public Library of Science (PLoS)
• Subjects: Analysis; Antibodies; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - pathology; Cell division; ErbB protein; ErbB-2 protein; Female; Gastric cancer; Gene expression; Gene set enrichment analysis; Humans; Kaplan-Meier Estimate; Lymph nodes; Medical prognosis; Medicine and Health Sciences; Menopause; Metastases; Mortality; mRNA; Multivariate analysis; Patients; Prognosis; Proteins; Regression analysis; Research and Analysis Methods; Ribonucleoside reductase; Ribonucleotide reductase; Signal transduction; Surgery; Survival; Survival analysis; Thyroid gland; Tumor cell lines; Tumors; Western blotting; China; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0265195

RRM2 plays an important role in different malignant tumors, but there are few studies in breast cancer. Public databases were used to analyze the expression of RRM2 in breast cancer and its prognostic value.
A total of 2,509 breast cancer samples were downloaded from the METABRIC database. The relationship between RRM2 expression and clinical pathology was evaluated. Using the BCIP database and real-time-PCR, and western blotting, RRM2 mRNA and protein expression of RRM2 in breast cancer tissues and cell lines were evaluated. Univariate and multivariate analysis defined independent prognostic factors that affected the overall survival of patients with breast cancer. The Kaplan-Meier method was used to study the relationship between the high expression of RRM2 and overall survival and distant metastasis-free survival (DMFS) of breast cancer patients. Finally, We performed Gene Set Enrichment Analysis (GSEA) and obtained the relevant pathways associated with high expression of RRM2 potentially influencing breast cancer progression.
RRM2 expression was significantly correlated with age, tumor size, grade, menopausal status, molecular typing, ER, PR, and Her-2 of patients with breast cancer(P<0.05). Univariate and multivariate regression analysis showed that RRM2, the number of positive lymph nodes, ER, Her-2, tumor size, and tumor stage can be used as independent prognostic factors for overall survival of patients with breast cancer. Kaplan-Meier analysis showed that in patients with Luminal A and Normal like breast cancers and Stage1 and stage2 breast cancers, patients with high expression of RRM2 had worse overall survival and DMFS. The analysis of the GSEA pathway showed that RRM2 is mainly enriched in the ERBB signaling pathway and other pathways.
The high expression of RRM2 has a worse prognosis in patients with breast cancer with specific features. It can be used as a biomarker for the prognosis of breast cancer.