PAFAH1B3 的增加与肝细胞癌的不良预后和 T 细胞衰竭微环境有关

Genhao Zhang
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摘要

肝细胞癌(HCC)中的T细胞衰竭(TEX)与PAFAH1B3之间的联系仍然未知,尽管两者都与总生存率有关。研究人员在TCGA和ICGC数据中调查了PAFAH1B3的表达,并使用50个配对的临床组织切片样本进行qRT-PCR和免疫组化(IHC)确认。免疫细胞丰度识别器(ImmuCellAI)用于精确计算TEX的丰度,其准确性通过单细胞RNA-seq和临床组织切片中CD8 + T细胞的标记得到了验证。IMVigor 210队列用于证明PAFAH1B3对免疫疗法疗效的预测价值。PAFAH1B3的增加是HCC患者预后不良的独立效应因子。PAFAH1B3水平较高的患者有更多的TEX浸润。在单细胞RNA-seq数据中,PAFAH1B3在TEX中的表达增加。PAFAH1B3高表达的患者更有可能对PD1/PD-L1治疗产生良好反应。总之,PAFAH1B3与肿瘤微环境(TME)中的TEX密切相关,可以作为PD1/PD-L1治疗的有用指标。
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Increased PAFAH1B3 was associated with poor prognosis and T-cell exhaustion microenvironment in hepatocellular carcinoma

The link between T-cell exhaustion (TEX) and PAFAH1B3 in hepatocellular carcinoma (HCC) remains unknown, even though both of them are related to overall survival. PAFAH1B3 expression was investigated in TCGA and ICGC data, and 50 paired clinical tissue section samples were used for qRT-PCR and immunohistochemistry (IHC) confirmation. The Immunocell Abundance Identifier (ImmuCellAI) was used to precisely calculate the abundance of TEX, and its accuracy was verified by single-cell RNA-seq and labeling of CD8 + T cells in clinical tissue sections. The IMVigor 210 cohort was used to demonstrate the predictive value of PAFAH1B3 for immunotherapy efficacy. Increased PAFAH1B3 is a standalone effector of poor prognosis in HCC patients. Patients who had greater PAFAH1B3 levels had more TEX infiltration. PAFAH1B3 expression was increased in TEX in the single-cell RNA-seq data. Patients with high PAFAH1B3 expression were more likely to respond favorably to PD1/PD-L1 treatment. In conclusion, PAFAH1B3 is closely related to TEX in the tumor microenvironment (TME) and can be a useful indicator for PD1/PD-L1 therapy.

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