WAKMAR2, a Prognosis-related Enhancer RNA in Gastric Cancer

Abstract Purpose An increasing number of long non-coding RNAs (lncRNAs) are thought to be associated with gastric cancer (GC). A lncRNA subclass that promotes enhancer function is called enhancer RNA (eRNA). We aimed to identify an eRNA that can predict GC prognosis and response to immune checkpoint inhibitors (ICIs).Methods Kaplan–Meier survival analysis was utilized to screen eRNA which can predict the prognosis of GC (P <0.05). The method of Spearman correlation analysis was employed in the filtration of target genes related to eRNA (r> 0.4, P <0.001). According to the median of WAKMAR2 expression, the patients were subdivided into low expression group and high expression group. Subsequently, differences of immune checkpoint-related genes and immune cell infiltration between the two groups were further explored. Furthermore, we analyzed the correlation of WAKMAR2 with tumor mutation burden (TMB) and microsatellite instability (MSI) in GC and other types of cancer.Results WAKMAR2 and its target gene TNFAIP3 entered the subsequent analysis. Patients with high-WAKMAR2 expression had a favorable prognosis compared to patients with low-WAKMAR2 expression (P = 0.048). Immune checkpoint-related genes (PD-L1, CTLA4, PDCD1, LAG3) in the WAKMAR2 high-expression group were also highly expressed, except for B7-H3. In addition, infiltration levels of B cells naive, T cells CD8, T cells CD4 memory activated, as well as Macrophages M1 in high-WAKMAR2 group were greater than in low-WAKMAR2 group. Last, the expression of WAKMAR2 in GC was significantly correlated with TMB and MSI.Conclusion WAKMAR2, a new eRNA, is a promising biomarker that can be used to predict the overall survival (OS) of GC patients, and WAKMAR2 expression can be utilized to identify ICB responders in GC, providing new insights for immunotherapy strategies.