Background: Glioma-associated oncogene homolog 1 (Gli1), affects the progression and the stemness characteristics of malignant carcinoma. The aim of the present study was to identify the relation between Glioma-associated oncogene homolog 1 (Gli1) and stemness and determine its clinical significance in gastric adenocarcinoma (GA). We investigated Gli1 expression and its correlation with other stemness-associated proteins in 169 GA samples and 5 GA cell lines.
Methods: To elucidate the role of Gli1 in the clinicopathological significance and stemness of GA, tissues samples from 169 GA patients were collected for immunohistochemistry (IHC). Additionally, MKN74, MKN28, NCI-N87, SNU638, AGS cells were collected for western blotting, MKN28 cells were collected for spheroid formation assay.
Results: Results showed that Gli1 expression was closely related to tumor grade, primary tumor (pT) stage, distant metastasis, clinical stage, gross type, microvessel density, and shorter overall survival (OS). Cox regression analysis verified that Gli1 was an independent prognostic factor for OS. Furthermore, Gli1 expression correlated with the expression of stemness-related genes, CD44, LSD1, and Sox9. Gli1 inhibitor GANT61 significantly decreased the expression of CD44 and LSD1, and spheroid formation ability of the MKN28 cells.
Conclusions: In conclusion, Gli1 may be a poor prognostic indicator and a potential cancer stemness-related protein in GA.
Keywords: Cancer stemness; Gastric adenocarcinoma; Glioma-associated oncogene homolog 1; Prognosis.