An immunohistochemical panel of three small ubiquitin-like modifier genes predicts outcomes of patients with triple-negative breast cancer

Yuxiang Lin; Qingshui Wang; Yingying Lin; Meichen Jiang; Han Xiao; Jie Zhang; Rongrong Guo; Shaohong Kang; Yao Lin; Chuangui Song

doi:10.21037/gs-21-37

An immunohistochemical panel of three small ubiquitin-like modifier genes predicts outcomes of patients with triple-negative breast cancer

Gland Surg. 2021 Mar;10(3):1067-1084. doi: 10.21037/gs-21-37.

Authors

Yuxiang Lin^{1

2

3}, Qingshui Wang^{4

5

6}, Yingying Lin⁷, Meichen Jiang⁸, Han Xiao⁸, Jie Zhang^{1

2

3}, Rongrong Guo^{1

2

3}, Shaohong Kang^{1

2

3}, Yao Lin^{4

5}, Chuangui Song^{1

2

3}

Affiliations

¹ Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
³ Breast Cancer Institute, Fujian Medical University, Fuzhou, China.
⁴ Central Laboratory at The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Collaborative Innovation Center for Rehabilitation Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
⁵ Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.
⁶ Fujian Provincial Key Laboratory of Hepatic Drug Research, Fuzhou, China.
⁷ Department of Healthcare, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁸ Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China.

Abstract

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 modifiers (SUMOs) mediate post-translational modifications (SUMOylation) has been shown to be involved in numerous biological processes. However, the role of SUMOylation in TNBC has yet to be elucidated.

Method: The mRNA expression of SUMO1/2/3 was analyzed by the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) databases (N=412). We also evaluated the SUMO1/2/3 protein expression in 212 TNBC patients using immunohistochemical (IHC) staining method. A classifier with Least absolute shrinkage and selection operator (LASSO) Cox regression model was then built based on the 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. With the LASSO model, we built a classifier based on the IHC scores of SUMO1/2/3 proteins and named it the 'SB classifier'. Patients with SB classifier-defined high score were found to have an unfavorable response to chemotherapy [hazard ratio (HR) 4.04, 95% confidence interval (CI): 2.14-7.63; P<0.0001]. A nomogram was then developed to identify which patients might benefit from chemotherapy. Finally, our results also suggested that the activation of SUMOylation pathway in TNBC might be induced by MYC signaling.

Conclusions: We constructed a reliable prognostic and predictive tool for TNBC patients treated with chemotherapy, which could facilitate individualized counseling and management.

Keywords: MYC; Triple-negative breast cancer (TNBC); chemotherapy; prognostic; small ubiquitin-like modifier (SUMO).