Identification of LETM1 as a marker of cancer stem-like cells and predictor of poor prognosis in esophageal squamous cell carcinoma.

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is closely related to the occurrence and development of malignant tumors. This study discusses the expression of LETM1 in esophageal squamous cell carcinoma (ESCC) and its association with cancer stem-like cells (CSC). We used immunohistochemistry in 166 ESCC tissue samples, as well as Western blot and immunofluorescent methods in ESCC cell lines, to study the role of LETM1 and its association with CSC in ESCC. The expression of LETM1 was significantly higher in ESCC, and it was closely related to the primary tumor stage and clinical stage. LETM1 expression was significantly associated with lower overall survival and disease-free survival. In addition, the protein expression of LETM1 and CSC markers was higher in TE11 and ECG10 than in other ESCC cell lines. Moreover, the expression of LETM1 positively correlated with LSD1, CD44, and OCT4. Immunofluorescence revealed that LETM1 costained with CD44 and OCT4 in ECG10. The expression of LETM1 was associated with not only HIF-1α but also higher microvessel density and tumor-associated macrophage infiltration. Furthermore, LETM1 significantly correlated with cyclinD1 and pAkt. High expression of LETM1 indicates poor prognosis and may be a potential CSC marker in ESCC. Moreover, LETM1 may be a novel therapeutic target for the treatment of ESCC.