High MAL2 expression predicts shorter survival in women with triple-negative breast cancer

Abstract

Introduction: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis.

Methods: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort.

Results: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort.

Conclusion: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Keywords: Biomarker; Breast cancer; MAL2; PD-L1; Prognosis; Survival; Triple-negative.

Fig. 1

Cross-section TNBC staining patterns: a H&E, b high MAL2 expression, c low MAL2 expression, d negative MAL2 expression, e negative PD-L1 expression, and f positive PD-L1 expression

Fig. 2

Patients’ survival depends on MAL2 status (89.59% vs. 71.33% 5 years after diagnosis in low-MAL2 and high-MAL2 groups, respectively; p = 0.0244)

Fig. 3

MAL2 and PD-1 are overexpressed in cancers compared to normal adjacent tissue (p = 0.0001 and p = 0.0007, respectively)

Fig. 4

Overall survival in the TCGA cohort based on MAL2 expression (p = 0.0001)

Fig. 5

Overall survival in the TCGA TNBC cohort based on MAL2 expression (p = 0.008)