Evaluation of immune-biomarker expression in high-grade soft-tissue sarcoma: HLA-DQA1 expression as a prognostic marker.
Evaluation of immune-biomarker expression in high-grade soft-tissue sarcoma: HLA-DQA1 expression as a prognostic marker.
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DOI：
10.3892/etm.2020.9225
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发表时间：
2020-11
影响因子：
2.7
通讯作者：
Kim JI
中科院分区：
文献类型：
--
作者：
Bae JY;Choi KU;Kim A;Lee SJ;Kim K;Kim JY;Lee IS;Chung SH;Kim JI
高级别软组织肉瘤（STS）是一种整体预后较差的高度恶性肿瘤。许多预后因素决定肿瘤进展和患者预后。在肿瘤微环境中发现的各种免疫相关细胞在各种肿瘤类型中发挥重要作用。本研究旨在评估免疫相关基因的表达，并阐明这些基因与高级别STS预后之间的关系。使用NanoString nCounter®系统对12个经福尔马林固定、石蜡包埋的高级别STS组织样本进行基因表达分析，另外35个样本进行免疫组织化学。为了进行比较分析，根据总生存期（OS）将患者分为两组。770个基因的表达水平首先使用nCounter®胰腺癌免疫分析小组进行分析。然后对改变最显著的基因进行免疫组化。随后，我们评估了基因表达与高级别STS预后的关系。在分析的770个免疫相关基因中，有几个基因在两组之间被确定为差异表达。根据基因表达水平和折叠变化，鉴定出13个有代表性的基因；13个候选基因中的7个（C3、CD36、DOCK9、FCER2、FOS、HLA-DRB4、NCAM1）在不良预后组中显著过表达，其余6个免疫相关基因（BIRC5、DUSP4、FOXP3、HLA-DQA1、HLA-DQB1、LAG3）在良好预后组中升高。免疫组化证实两组间13个免疫相关基因的表达有显著差异。HLA-DQA1、HLA-DQB1和HLA-DRB4分别在74.3%、34.3%和48.6%的肿瘤中表达。不良预后组HLA-DQA1和HLA-DQB1显著降低，而HLA-DRB4显著升高。值得注意的是，HLA-DQA1的表达与较长的OS相关（P=0.028）。总之，HLA-DQA1表达与长期生存显著相关，因此可能是高级别STS预后良好的免疫生物标志物。
High-grade soft-tissue sarcoma (STS) is a highly malignant neoplasm with a poor overall prognosis. Numerous prognostic factors determine tumor progression and patient outcomes. Various immune-associated cells identified in the tumor microenvironment have important roles in various tumor types. The present study was performed to evaluate the expression of immune-associated genes and to elucidate the association between these genes and the prognosis in high-grade STS. A total of 12 formalin-fixed, paraffin-embedded tissue samples of high-grade STS were subjected to gene expression analysis using the NanoString nCounter® System and another 35 samples were used for immunohistochemistry. For comparative analysis, the patients were divided into two groups according to overall survival (OS). The expression levels of 770 genes were first analyzed using the nCounter® PanCancer Immune Profiling Panel. Immunohistochemistry was then performed for the most significantly altered genes. Subsequently, the association between gene expression and prognosis of high-grade STS was evaluated. Of the 770 immune-associated genes analyzed, several genes were identified as being differentially expressed between the two groups. Based on gene expression levels and fold change, 13 representative genes were identified; 7 of the 13 candidate genes (C3, CD36, DOCK9, FCER2, FOS, HLA-DRB4 and NCAM1) were significantly overexpressed in the poor prognosis group, while the other 6 immune-associated genes (BIRC5, DUSP4, FOXP3, HLA-DQA1, HLA-DQB1 and LAG3) were increased in the good prognosis group. By immunohistochemistry, the expression of the 13 immune-associated genes was confirmed to be significantly different between the two groups. Expression of HLA-DQA1, HLA-DQB1 and HLA-DRB4 was observed in 74.3, 34.3 and 48.6% of tumors, respectively. HLA-DQA1 and HLA-DQB1 were significantly decreased, whereas HLA-DRB4 was significantly increased in the poor prognosis group. Of note, expression of HLA-DQA1 was associated with a significantly longer OS (P=0.028). In conclusion, HLA-DQA1 expression was significantly associated with long-term survival and may therefore be an immune biomarker for good prognosis in high-grade STS.
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通讯作者：
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影响因子：
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影响因子：
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作者：
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