Abstract
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.
Highlights
Metabolic syndrome (MetS) represents a cluster of metabolic disorders, including obesity, hyperglycemia, hypertension, and dyslipidemia
The multivariate Cox analysis demonstrated that MetS was an independent factor (HR = 2.21; 95% confidence intervals (CIs): 1.27–3.86; p = 0.005)
We found that N stage, history of adjuvant therapy, hyperglycemia, T stage, and TNM stage were associated with Recurrence-free survival (RFS) in univariate analysis, and MetS (HR =1.71; 95% CI: 0.99–2.96; p = 0.0554) influenced the RFS of patients
Summary
Metabolic syndrome (MetS) represents a cluster of metabolic disorders, including obesity, hyperglycemia, hypertension, and dyslipidemia. A recent study showed a high prevalence of MetS at 33.9% (31% in men and 36.8% in women), with a dramatic increase from 2000 to 2010 in China [3]. MetS is an embodiment of comprehensive effects and is associated with multiple diseases, including tumors [4, 5]. The presence of MetS can increase the risk and influence the prognosis of various tumors, such as colorectal cancer, breast cancer, and prostate cancer [6,7,8]. 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
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