Abstract: Objective To investigate the expression, function and prognostic value of Ras-related C3 botulinum toxin substrate 2(RAC2) in breast cancer. Methods The expression profile of RAC2 mRNA was investigated in the TCGA-BRCA cohort,the prognostic value was analyzed using the Kaplan-Meier algorithm,the potential molecular function was investigated by gene set enrichment analysis,the relationship between RAC2 and immune infiltration was analyzed by Estimate and Cibersort algorithms,and the association between Rac2 and mutation spectrum was evaluated by maftools software package.The RNA-seq software package “pRRophetic” was used to predict the effect of chemotherapy drugs.In the validation cohort,Immunohistochemistry (IHC) staining was performed on tumor pathological sections of patients.Kaplan-Meier survival analysis and cox regression analysis were used to analyze the relationship between RAC2 and the prognosis of breast cancer. Results Bioinformatics analysis showed that the expression of RAC2 was up-regulated in estrogen receptor (ER) positive BC. In the Pam50 molecular subtype of BC, its expression decreased in the order of normal-like group, triple negative group, HER2 overexpression group, Luminal A group and Luminal B group. BC patients with high RAC2 expression had better overall survival (OS) and recurrence-free survival (RFS). The results of the validation cohort confirmed that RAC2 can be used as an independent predictor of BC prognosis. RAC2 was involved in the process of immune infiltration of tumor cells, and its high expression was mainly related to the mutations of CCDC168, VPS13C and AHNAK genes. Its up-regulation increased the drug sensitivity of doxorubicin, cisplatin, paclitaxel and gemcitabine. In terms of metabolism, it was negatively correlated with glycolysis and pentose phosphate pathway(PPP), and positively correlated with fatty acid oxidation (FAO) and glutamine metabolism. Conclusion High expression of RAC2 is associated with a good prognosis of BC and plays a role in the metabolism and immune infiltration. Further study on the molecular mechanism of RAC2 may provide new strategies for the prognosis and treatment of BC.

Key words: Rasrelated C3 botulinum toxin substrate 2 (RAC2), breast cancer, prognosis, survival analysis, immunity, metabolism