Abstract
Background: High-grade soft tissue sarcoma (STS) is a highly malignant neoplasm having an overall poor prognosis. Numerous prognostic factors determine tumor progression and patient outcome. Many immune-related cells identified in the tumor microenvironment play important roles in various tumor types. This study was undertaken to evaluate the expression of immune-related genes and to elucidate the correlation between these genes and prognosis in high grade STS.Methods: Twelve cases of formalin-fixed paraffin embedded tissue samples of high grade STS were included for gene expression analysis using the NanoString nCounter® System and 35 cases were used for immunohistochemistry. For comparison analysis, the patients were divided into two groups, depending on the overall survival (OS). Expressions of 770 Genes were analyzed using the nCounter® PanCancer Immune Profiling Panel of the NanoString nCounter® Analysis System. Immunohistochemistry for the most significantly altered genes was additionally performed. The correlation between gene expression and prognosis of high grade STS was then evaluated.Results: Of the 770 immune-related genes analyzed by NanoString nCounter® Analysis, several genes were identified as differentially expressed between the two groups. Based on the gene expression level and fold change, representative 13 genes were identified: 7 of the 13 candidate genes (C3, CD36, DOCK9, FCER2, FOS, HLA-DRB4, and NCAM1) were found to be significantly overexpressed in the poor prognostic group. In contrast, expressions of the other 6 immune-related genes (BIRC5, DUSP4, FOXP3, HLA-DQA1, HLA-DQB1, and LAG3) were increased in the good prognostic group. Positive expressions of HLA-DQA1, HLA-DQB1, and HLA-DRB4 were obtained in 74.3%, 34.3% and 48.6% tumors, respectively. The positive expression of HLA-DQA1 was associated with a significantly longer OS (p=0.028). .Conclusions: Analysis of gene expression determined that expressions of 13 immune-related genes were significantly different between two groups. HLA-DQA1 and HLA-DQB1 were significantly decreased, whereas HLA-DRB4 was significantly increased in the poor prognostic group. HLA-DQA1 expression was significantly correlated with long-term survival, and may therefore be an immune-biomarker for good prognosis of high grade STS.
Evaluation of immune‑biomarker expression in high‑grade soft‑tissue sarcoma: HLA‑DQA1 expression as a prognostic marker
