An Immunohistochemical Panel of Three SUMO Genes Predicts Outcomes of Patients With Triple-negative Breast Cancer

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease. Developing new candidate biomarkers for chemotherapy response and possible therapeutic targets has become an urgent clinical need. Small ubiquitin-like modifier (SUMOs) mediate post-translational modifications (SUMOylation) that target multiple proteins was involved in many biological processes. The role of SUMOylation in TNBC remains to be elucidated. Method: The expression of SUMO1/2/3 were analyzed using TCGA and GEO databases (N=412). We also evaluated the SUMO1/2/3 protein expression in 212 local TNBC patients using immunohistochemical (IHC) staining. We then built a classifier with the LASSO Cox regression model based on associations between the expression of SUMO1/2/3 proteins and the disease-free survival (DFS) of TNBC patients. Results: : Elevated SUMO1/2/3 levels were indicated to be associated with a poorer overall survival (OS) and DFS for TNBC patients. Using the LASSO model, we built a classifier based on the IHC scores of SUMO1/2/3 proteins and named it ‘SB classifier’. Patients with the SB classifier defined high score were found to have an unfavorable response to chemotherapy (HR 4.04, 2.14-7.63; p <0.0001). We then developed a nomogram to predict which patients might benefit from chemotherapy. Finally, our analysis provides insights on possible mechanisms that MYC activation causes the activation of SUMOylation. Conclusion: We constructed a reliable prognostic and predictive tool for TNBC patients treated with chemotherapy. It may facilitate patient counseling and individualize management of TNBC patients. Meanwhile, our results suggested that the activation of SUMOylation pathway in TNBC may be induced by MYC signaling.