Identification of a TLR-Induced Four-lncRNA Signature as a Novel Prognostic Biomarker in Esophageal Carcinoma

Long non-coding RNAs (lncRNAs) have emerged as key regulators of Toll-like receptor (TLR) signaling to control innate immunity, and this regulatory mechanism has recently been implicated in esophageal carcinoma (ESCA). However, a comprehensive analysis of TLR-induced lncRNAs and their roles in diagnosis and prognosis in ESCA is still lacking. In this study, we first investigated the precise relationship between lncRNA perturbations and alteration of TLR signaling by constructing the lncRNA-TLRs co-expression network involved in ESCA, and identified 357 TLR-related lncRNAs. Of them, four TLR-related lncRNAs (AP000696.1, LINC00689, LINC00900, and AP000487.1) are significantly associated with the overall survival (OS) of ESCA patients, and utilizing this four-lncRNA signature is capable of stratifying patients into high-risk and low-risk groups with significantly different OS in the discovery set. Further analysis in different independent patient sets also confirmed the robustness of the prognostic value of the four-TLR-lncRNA signature in predicting the OS of ESCA patients. Moreover, the results of multivariate analysis in different patient sets indicated that the four-TLR-lncRNA signature is an independent factor after adjusted by other clinical factors. Thus, we have identified a TLR-induced four-lncRNA signature, which represents a promising prognosis biomarker for ESCA, and our study might provide new candidate targets for therapeutic intervention via targeting TLR-induced lncRNAs in ESCA patients.