Differential expression of long non-coding RNA HOTAIR in intestinal metaplasia and gastric cancer

Abstract

Introduction: High expression of HOTAIR promotes tumor growth and carries a dismal prognosis for the patient. We investigated the prognostic value of HOTAIR expression in gastric cancer (GC) and systematically delineate the expression in relation to Helicobacter pylori (H. pylori) infection and preneoplastic changes.Methods: HOTAIR expression was analyzed in surgical paired tissue samples of GC patients and biopsy samples from patients with atrophic gastritis and/or intestinal metaplasia (AG+/-IM), chronic non-atrophic gastritis (CNAG), and controls. TCGA data was used for validation. HOTAIR expression was evaluated in sera and ascites of GC patients. Quantitative HOTAIR expression analysis was performed using qPCR and LINE-1 methylation was assessed by bisulfite pyrosequencing.Results: HOTAIR was more frequently detected in tumor tissues compared to adjacent gastric mucosa (65.4% vs 8.6%). HOTAIR expression was associated with depth of tumor invasion and tumor location and with shorter overall survival in diffuse-type GC patients as confirmed in TCGA cohort. HOTAIR was not detectable in controls, but was found in 2.2% of CNAG patients and 18.3% of patients with AG+-/IM which was further associated with IM, grade of IM and H. pylori positivity. Discussion: HOTAIR expression was associated with GC and preneoplastic changes of stomach mucosa. Although, HOTAIR expression was strongly linked to IM, HOTAIR expression was only associated with worse prognosis in Lauren´s diffuse and not intestinal type of GC. Further studies are needed to evaluate the value of HOTAIR as diagnostic and predictive biomarker in IM and translational therapeutic relevance of HOTAIR in diffuse type GC.