Clinical implication of leucine zipper/EF hand-containing transmembrane-1 overexpression in the prognosis of triple-negative breast cancer

Abstract Triple negative breast cancer (TNBC) is a heterogeneous disease with higher rates of relapse and decreased overall survival in metastatic tumors. Due to its poor prognosis, it is necessary to identify effective biomarkers that are associated with tumor growth and metastasis. The leucine zipper/EF hand-containing transmembrane-1 (LETM1) protein, which is a mitochondrial inner membrane protein, can reduce mitochondrial biogenesis and ATP production. The expression levels of LETM1 were significantly increased in numerous human malignancies. However, the clinicopathological characteristics and prognostic value of LETM1 overexpression in TNBC remains unclear. LETM1 protein was detected in 107 TNBC, 42 ductal carcinoma in situ (DCIS) and 65 adjacent non-tumor breast tissues using immunohistochemical (IHC) staining. Immunofluorescence (IF) staining was also performed to detect the localization of LETM1 protein in MCF-7 BC cells. The correlations between LETM1 overexpression and clinicopathological features of TNBC were evaluated using Chi-squared test and Fisher's exact tests. The survival rate was calculated using the Kaplan–Meier method. LETM1 protein showed cytoplasmic staining patterns in TNBC. The strongly positive rate of LETM1 in TNBC was 69.2% (74/107), which was significantly higher than in both DCIS 35.7% (15/42) and adjacent non-tumor tissues 12.3% (8/65). High-level expression of LETM1 was positively correlated with late clinical stage, poor differentiation, lymph node metastasis, disease-free survival (DFS) and 10-year overall survival (OS) rates in TNBC. Further analysis showed that high LETM1 expression along with clinical stage emerged as significant independent risk factors in patients with TNBC. In conclusion, LETM1 protein overexpression is associated with TNBC progression, and may be a potential biomarker for poor prognostic evaluation of TNBC.