A vasculogenic mimicry prognostic signature associated with immune signature in human gastric cancer.

A vasculogenic mimicry prognostic signature associated with immune signature in human gastric cancer.
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与人类胃癌免疫特征相关的血管生成拟态预后特征

DOI:
10.3389/fimmu.2022.1016612
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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胃癌是世界范围内死亡率最高的恶性肿瘤之一,预后差。血管拟态(VM)是一种不依赖于内皮细胞或血管生成的肿瘤替代血液供应。已有研究表明VM与胃癌患者预后不良有关,但VM与胃癌免疫浸润的关系及其机制尚不清楚。在这项研究中,从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中检索VM相关基因的表达谱。进行考克斯回归以鉴定与存活率相关的关键VM相关基因。在此基础上,提出了一种新的GC风险评分模型VM指数和诺模图。此外,一个关键的VM相关基因(丝氨酸蛋白酶抑制剂家族F成员1,SERPINF 1)的表达进行了验证,在33个GC组织和23个癌旁组织中使用免疫组化染色。单因素和多因素考克斯回归分析显示,SERPINF 1和组织因子途径抑制物2(TFPI 2)是影响胃癌患者预后的独立危险因素。AUC(> 0.7)表明诺模图具有良好的区分能力。SsGESA和ESTIMATE结果显示SERPINF 1和TFPI 2的高表达与胃癌的免疫浸润有关。免疫组织化学染色证实SERPINF 1蛋白在胃癌组织中的表达明显高于癌旁组织。一个VM指数和诺模图的构建,并表现出令人满意的预测性能。此外,VM被证实广泛参与免疫浸润,这表明VM可能是一个有前途的靶点,在指导免疫治疗。综上所述,我们确定SERPINF1和TFPI 2为与GC VM相关的免疫学和预后生物标志物。
Gastric cancer (GC) is one of the most lethal malignant tumors worldwide with poor outcomes. Vascular mimicry (VM) is an alternative blood supply to tumors that is independent of endothelial cells or angiogenesis. Previous studies have shown that VM was associated with poor prognosis in patients with GC, but the underlying mechanisms and the relationship between VM and immune infiltration of GC have not been well studied. In this study, expression profiles from VM-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cox regression was performed to identify key VM-related genes for survival. Subsequently, a novel risk score model in GC named VM index and a nomogram was constructed. In addition, the expression of one key VM-related gene (serpin family F member 1, SERPINF1) was validated in 33 GC tissues and 23 paracancer tissues using immunohistochemistry staining. Univariate and multivariate Cox regression suggested that SERPINF1 and tissue factor pathway inhibitor 2 (TFPI2) were independent risk factors for the prognosis of patients with GC. The AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. SsGESA and ESTIMATE showed that higher expression of SERPINF1 and TFPI2 is associated with immune infiltration of GC. Immunohistochemistry staining confirmed that the expression of SERPINF1 protein was significantly higher in GC tissues than that in paracancer tissues. A VM index and a nomogram were constructed and showed satisfactory predictive performance. In addition, VM was confirmed to be widely involved in immune infiltration, suggesting that VM could be a promising target in guiding immunotherapy. Taken together, we identified SERPINF1 and TFPI2 as immunologic and prognostic biomarkers related to VM in GC.
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