title: 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.
authors.affiliation: Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: suefordking@163.com.
authors.forename: Chang-an
authors.initials: CA
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China; Department of Pathology, Yanbian University Medical College, Yanji 133002, China. Electronic address: 2293380@163.com.
authors.forename: Qixiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: yunboch@163.com.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Yanbian University Medical College, Yanji 133002, China. Electronic address: liushp@ybu.edu.cn.
authors.forename: Shuangping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: jingweix2000@163.com.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, Yanbian University Medical College, Yanji 133002, China. Electronic address: 592362250@qq.com.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China. Electronic address: chzhangyan@medmail.com.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Yanbian University Hospital, Yanji 133000, China. Electronic address: plz1978@126.com.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Piao
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D020832:EF Hand Motifs; D005260:Female; D006801:Humans; D016350:Leucine Zippers; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D051336:Mitochondrial Membranes / Q000473:pathology; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D064726:Triple Negative Breast Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C488528:LETM1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins
keywords: Biomarker; LETM1; Prognosis; Triple negative breast cancer