Abstract
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.
Highlights
Breast cancer has become the leading cause of global cancer in 2020, accounting for 11.7% of all new cases of malignant tumors
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
The high expression of RRM2 has a worse prognosis in patients with breast cancer with specific features
Summary
Breast cancer has become the leading cause of global cancer in 2020, accounting for 11.7% of all new cases of malignant tumors. Among female patients with malignant tumors, the incidence rate is 24.5%, and the mortality rate is 15.5%, both ranking first among cancers [1]. Studies have shown that gene mutations and gene disorders are the main reasons leading to the occurrence and development of many cancers [4]. The differential expression of RRM2 is closely related to the occurrence, development, and prognosis of pancreatic cancer, gastric cancer, non-small cell lung cancer, liver cancer, malignant endometriosis, and other tumors [5–10]. It is very important to find new biomarkers and therapeutic targets that affect the survival and prognosis of breast cancer. 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
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