Elevated SYNC Expression Is Associated with Gastric Tumorigenesis and Infiltration of M2-Polarized Macrophages in the Gastric Tumor Immune Microenvironment

Genet Test Mol Biomarkers. 2021 Mar;25(3):236-246. doi: 10.1089/gtmb.2020.0131.

Abstract

Aims: To assess the expression and epigenetic regulation of Syncoilin, intermediate filament protein (SYNC) in gastric cancer tissues, and to determine its associations with clinicopathological features; immune infiltration of macrophages in tumors; and patient survival. Materials and Methods: Clinicopathological features, expression profiles, and methylation data of the SYNC gene were obtained from multi-institutional real-world public datasets. A total of 1601 samples from patients with gastric cancer were examined. The associations between clinicopathological features and SYNC expression levels were assessed by the chi-square test; survival was assessed using the Kaplan-Meier analysis. The infiltration levels of M1, 2-polarized tumor-associated macrophages (TAMs) in a gastric tumor immune microenvironment were quantified using deconvolution, and the correlation between SYNC expression level and M1, 2-polarized macrophages' infiltration was examined using the Pearson correlation test. SYNC gene methylation data were analyzed to investigate epigenetic control of its expression. Results: SYNC expression was elevated in gastric cancer tissues (p < 0.01), and was associated with a poorer overall survival (p < 0.01) and poorer postprogression survival (p = 0.01). Higher SYNC levels were significantly associated with more aggressive clinicopathological features in gastric cancer patients (p < 0.05). SYNC was also associated with the infiltration of M2-polarized TAMs in the gastric tumor immune microenvironment (p < 0.001). Hypomethylation was shown to be associated with SYNC's upregulation (p < 0.05). Conclusion: SYNC is highly expressed in gastric cancer tissues and has the potential to be a therapeutic target and to serve as a prognostic marker.

Keywords: SYNC (Syncoilin intermediate filament protein); cancer biomarkers; gastric carcinoma; prognosis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / immunology
  • China
  • DNA Methylation
  • Databases, Genetic
  • Epigenesis, Genetic / genetics
  • Epigenomics / methods
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Prognosis
  • Stomach / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • Intermediate Filament Proteins
  • Muscle Proteins
  • SYNC protein, human