LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma

Abstract

The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is highly expressed in many human malignancies and is correlated with poor prognosis. However, LETM1 has rarely been explored as a cancer stem-like cell marker for the prognostic evaluation of colorectal adenocarcinoma (CRA). Herein, we assessed the expression of LETM1 and its relationship with cancer stemness genes, cell cycle markers, PI3K/Akt/NFκB signaling pathway genes, and HIF1α in 102 paraffin-embedded CRA tissue samples using immunohistochemistry (IHC). Additionally, we further confirmed the correlation between LETM1 and cancer stemness genes in CRA cell lines using immunofluorescence (IF) imaging and Western blotting. LETM1 expression was remarkably upregulated in human fetal sagittal sections and CRA tissues. The expression of LETM1 in CRA tissue was correlated with clinical stage, lymph node metastasis, distant metastasis, and microvessel density. LETM1 expression was significantly associated with lower overall survival and disease-free survival. Moreover, the expression of LETM1 positively correlated with SOX9, LSD1, CD44, CD133, LGR5, SOX2, and HIF1α. IF revealed that LETM1 co-localized with CD44, SOX9, and LGR5 in HCT116. Moreover, LETM1 expression was also strongly linked to the expression of cell cycle regulators (cyclinD1, CDK4, p27) and PI3K/Akt/NFκB pathway genes (pPI3K-p85, pAkt-Ser473, pAkt-Thr308, pNFκB-p65). LETM1 may therefore be a cancer stem-like cell marker and an indicator of poor prognosis in patients with CRA.