Abstract

BackgroundGlioma-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.MethodsTo 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.ResultsResults 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.ConclusionsIn conclusion, Gli1 may be a poor prognostic indicator and a potential cancer stemness-related protein in GA.

Highlights

  • Glioma-associated oncogene homolog 1 (Gli1), affects the progression and the stemness characteristics of malignant carcinoma

  • Association between the expression of Gli1 and clinical characteristics of gastric adenocarcinoma (GA) To understand if Gli1 is associated with GA progression, we investigated Gli1 expression in human GA by a Tissue Microarray (TMA) analysis

  • Our results find a correlation between Gli1 expression and primary tumor (pT) stage and distant metastasis, but no correlation with tumor size or lymph node metastasis

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Summary

Introduction

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 Gliomaassociated oncogene homolog 1 (Gli1) and stemness and determine its clinical significance in gastric adenocarcinoma (GA). It was found that the 5-year survival rate for patients with early stage GA is approximately 90%, but it decreases to 16.6% for patients with advanced GA [1]. There are many treatments for advanced GA, the overall survival (OS) is still poor. Cancer stem-like cells (CSCs) maintain the viability of the cancer cell population through self-renewal and infinite proliferation, and play an important role in survival, proliferation, metastasis, and tumor recurrence. CSCs are viewed as novel therapeutic targets due to their stemness potential [2].

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