PDIA3 correlates with clinical malignant features and immune signature in human gliomas
PDIA3 correlates with clinical malignant features and immune signature in human gliomas
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PDIA3 与人类神经胶质瘤的临床恶性特征和免疫特征相关。
DOI：
10.18632/aging.103601
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发表时间：
2020-08-15
期刊：
影响因子：
5.2
通讯作者：
Cao, Hui
中科院分区：
文献类型：
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作者：
Zhang, Hao;Zhou, Yulai;Cao, Hui
由于胶质瘤的治疗策略有限，因此新的分子或生物标志物对于诊断和治疗至关重要。在这里，我们研究了蛋白质二硫键异构酶家族A成员3（PDIA 3）在胶质瘤中的表达，以评估其作为一个有前途的免疫靶点或生物标志物的潜力。从TCGA和CGGA数据库中分析转录组水平、基因组谱及其与临床实践的关联。所有统计分析均使用R项目进行。在PDIA 3高表达的胶质瘤中，体细胞突变与PTEN缺失和EGFR扩增相关;而在PDIA 3低表达的胶质瘤中，异柠檬酸脱氢酶（IDH）突变占80%。此外，发现PDIA 3与ESTIMATE评分和定位于肿瘤微环境中的多种浸润性免疫和基质细胞类型正相关。基于单细胞测序发现PDIA 3与巨噬细胞和T细胞高度相关。此外，PDIA 3还通过多种免疫调节过程参与抑制抗肿瘤免疫。最后，观察到PDIA 3与其他免疫检查点抑制剂相关，并与炎症相关。我们的研究结果证实了PDIA 3在胶质瘤发生发展过程中的重要性，并证明了PDIA 3作为胶质瘤预后和免疫相关治疗的分子靶点的潜力
Since therapeutic strategies are limited in gliomas, new molecules or biomarkers are essential for diagnosis and therapy. Here, we investigated expression of protein disulfide isomerase family A member 3 (PDIA3) in gliomas to evaluate its potential as a promising immune target or biomarker. Transcriptome level, genomic profiles and its association with clinical practice from TCGA and CGGA databases were analyzed. All statistical analyses were performed using R project. In gliomas with high PDIA3 expression, somatic mutations showed the correlation with loss of PTEN and amplification of EGFR; meanwhile, in PDIA3 low gliomas, mutations in isocitrate dehydrogenase (IDH) took 80%. Moreover, PDIA3 was found to positively correlate with ESTIMATE scores and diverse infiltrating immune and stromal cell types localizing in tumor microenvironment. PDIA3 was found to be highly correlated with macrophage and T cells based on single cell sequencing. Additionally, PDIA3 was also involved in suppression of anti-tumor immunity via multiple immune regulatory processes. Finally, PDIA3 was observed to correlate with other immune checkpoint inhibitors and associated with inflammation. Our findings identified the significance of PDIA3 in the process of gliomas and demonstrated the potential of PDIA3 as a molecular target in prognosis and immune related treatment of gliomas