间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:PCDHGA10 as a potential prognostic biomarker and correlated with immune infiltration in gastric cancer.
PCDHGA10 as a potential prognostic biomarker and correlated with immune infiltration in gastric cancer.
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PCDHGA10 可能是 GC 的潜在预后标志物和免疫治疗靶点。
胃癌(GC)是最常见的恶性肿瘤之一,预后较差。为了改善GC患者的预后,迫切需要一种有效的免疫相关预后生物标志物。在此,我们旨在探讨降钙素原γ亚家族A成员10(PCDHGA10)的表达与临床病理特征之间的相关性,尤其是其与GC中肿瘤浸润免疫细胞(TILs)的关系。
通过癌症基因组图谱(TCGA)评估了PCDHGA10在GC组织与正常胃黏膜之间的mRNA差异表达及预后潜力。随后,基于GC患者的组织微阵列(TMAs)和多重免疫组化(mIHC),我们统计评估了PCDHGA10蛋白表达与患者临床特征及预后之间的相关性。此外,利用IHC和mIHC,我们应用机器学习算法评估了肿瘤微环境中TILs和免疫检查点的定位及表达水平。我们分析了PCDHGA10蛋白表达与TILs及免疫检查点之间的关系。
通过数据库和TMA分析,PCDHGA10在GC组织中的表达显著高于正常组织。PCDHGA10高表达独立预测GC不良预后。此外,PCDHGA10表达升高与GC组织和基质区域中CD8 + T细胞、CD68 + 巨噬细胞、Foxp3 + T细胞和CD4 + T细胞数量呈正相关。此外,PCDHGA10的表达与免疫检查点(包括CTLA-4、LAG3和PD-L1)呈正相关。
Gastric cancer (GC) is one of the most common malignant tumors and is associated with poor prognosis. To improve the prognosis of GC patients, an effective immune-related prognostic biomarker is urgent. Here, we aim to explore the correlation between the expression of procalcitonin gamma subfamily A, 10 (PCDHGA10) and clinicopathological characteristics, especially its relation with tumor-infiltrating immune cells (TILs) in GC.
The differential mRNA expression of PCDHGA10 between GC tissues and normal gastric mucosa and prognostic potential were assessed from The Cancer Genome Atlas (TCGA). Then, based on tissue microarrays (TMAs) with multiplex immunohistochemistry (mIHC) from GC patients, we statistically assess the correlation between PCDHGA10 protein expression and the clinical profiles and prognosis of the patients. Additionally, with IHC and mIHC, we applied the machine-learning algorithms to evaluate the localization and expression levels of TILs and immune checkpoints in the tumor microenvironment. We analyzed the relationship between PCDHGA10 protein expression and TILs and immune checkpoints.
Through the database and TMA analysis, the expression of PCDHGA10 was significantly higher in GC tissues compared with normal tissues. High PCDHGA10 expression independently predicted poor prognosis in GC. Additionally, elevated PCDHGA10 expression was positively associated with the number of CD8 + T cells, CD68 + macrophages, Foxp3 + T cells, and CD4 + T cells in GC tissues and the stromal region. Besides, the expression of PCDHGA10 was positively correlated with immune checkpoints, including CTLA-4, LAG3, and PD-L1.
PCDHGA10 might be a potential prognostic marker and an immunological therapeutic target for GC.
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