The Prognostic Significance of Metabolic Syndrome and a Related Six-lncRNA Signature in Esophageal Squamous Cell Carcinoma

Background: Metabolic syndrome (MetS) is associated with the development of esophageal squamous cell carcinoma (ESCC), and long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms of MetS and tumor. This study will explore the prognostic effect of MetS and the associated lncRNA signature on ESCC. Methods: Our previous RNA-chip data (GSE53624, GSE53622) for 179 ESCC patients were reanalyzed according to MetS. The recurrence-free survival (RFS) was collected for these patients. The status of the MetS-related tumor microenvironment was analyzed with the CIBERSORT and ESTIMATE algorithms. A lncRNA signature was established with univariate and multivariate Cox proportional hazards regression (PHR) analysis and verified using the Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic (ROC) curves. A clinical predictive model was constructed based on multiple risk factors, evaluated using C-indexes and calibration curves, and verified using data from the GEO and TCGA databases. Results: The results showed that MetS was an independent risk factor for ESCC patients conferring low OS and RFS. Tumor microenvironment analysis indicated that patients with MetS have high stromal scores and M2 macrophage infiltration. A six-lncRNA signature was established by 60 ESCC patients randomly selected from GSE53624 and identified with an effective predictive ability in validation cohorts (59 patients from GSE53624 and 60 patients from GSE53622), subgroup analysis, and ESCC patients from TCGA. MetS and the six-lncRNA signature could be regarded as independent risk factors and enhanced predictive ability in the clinical predictive model. Conclusions: Our results indicated that MetS was associated with poor prognosis in ESCC patients, and the possible mechanism was related to changes in the tumor microenvironment. MetS and the six-lncRNA signature could also serve as independent risk factors with available clinical application value.