LINC01094 Predicts Poor Prognosis in Patients With Gastric Cancer and is Correlated With EMT and Macrophage Infiltration

Abstract

Objectives: The novel long non-coding RNA (lncRNA) LINC01094 is often upregulated in renal cell carcinoma and glioma; however, its role in gastric cancer remains unclear. Here, we aim to demonstrate the relationship between LINC01094 and gastric cancer. Method: The gene expression (RNASeq) data of 375 patients with localized, locally advanced, and metastatic gastric cancer were extracted from The Cancer Genome Atlas. The Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between the clinicopathological characteristics and LINC01094 expression. Cox regression analysis and the Kaplan–Meier method were used to assess prognostic factors of gastric cancer. A nomogram based on Cox multivariate analysis was used to predict the impact of LINC01094 on gastric cancer prognosis. Gene set enrichment analysis (GSEA) was used to identify key LINC01094-associated signaling pathways. Fluorescence in situ hybridization (FISH) was performed to detect the location of LINC01094 in the tissue, and a competing endogenous (ce)RNA network was constructed to identify LINC01094-related genes. Spearman's rank correlation was used to elucidate the association between LINC01094 expression level and immune cell infiltration level. Result: LINC01094 expression was upregulated in gastric cancer tissues and strongly associated with overall survival using univariate Cox regression (hazard ratio [HR]  =  1.476, 95% CI  =  1.060-2.054, P  =  .021) and multivariate Cox regression analysis (HR  =  1.535, 95% CI  =  1.021-2.308, P  =  .039). The area under the receiver operating characteristic curve of LINC01094 was 0.910. GSEA showed a strong relationship between LINC01094 and the epithelial-mesenchymal transition pathway. RNA-FISH demonstrated that LINC01094 localized in the cytoplasm. It was closely related to the epithelial-mesenchymal transition (EMT) marker SNAI2, according to ceRNA ( R  =  0.61, P < .001), and macrophage-related gene FCGR2A. Macrophages were also significantly positively correlated with LINC01094 expression ( R  =  0.747, P < .001). Conclusion: High LINC01094 expression predicts poor prognosis in gastric cancer and is correlated with the epithelial-mesenchymal transition pathway and macrophage infiltration.