LETM1 is a potential biomarker that predicts poor prognosis in gastric adenocarcinoma.

In this study, we assessed the expression of LETM1 along with the genes related to cancer stemness, cell cycle, and PI3K/Akt signaling in 189 paraffin-embedded GA tissue samples and GA-derived cell lines using immunohistochemistry (IHC), western blotting, and immunofluorescence. Our results showed that the expression of LETM1 was strongly correlated with the tumor grade, primary tumor (pT) stage, lymph node metastasis, clinical stage, and tumor gross type of GA. The Kaplan-Meier survival analysis revealed that patients with GA with high expression of LETM1 exhibit a shorter overall survival (OS) rate. Univariate and multivariate Cox regression analysis indicated that LETM1 is an independent poor prognostic factor of GA. Significantly, LETM1 expression was positively correlated with the expression of cancer stemness-related genes such as CD44 and LGR5 and expression of cell-cycle related gene, cyclin D1. Further, the expression of proteins involved in PI3K/Akt signaling pathway, such as pPI3K-p85 and pAkt-Thr308, was also increased. Additionally, small interfering RNA (esiRNA)-mediated silencing of LETM1 expression in GA-derived cell lines MKN28 and MKN74 strongly inhibited the expression of stemness and cell cycle-related proteins, suppressed cancer cell spheroid formation, migration and invasion ability, and affected cell cycle distribution. Furthermore, the GA-derived cell line AGS exhibited enhanced expression of LETM1, CD44, LGR5, and HIF1-α under hypoxic conditions. Las...
Source: Experimental and Molecular Pathology - Category: Pathology Authors: Tags: Exp Mol Pathol Source Type: research