Apolipoprotein B Is Associated With the Microenvironment of Cholangiocarcinoma.
Apolipoprotein B Is Associated With the Microenvironment of Cholangiocarcinoma.
复制标题
载脂蛋白B与胆管癌的微环境有关
DOI：
10.3389/fonc.2021.654689
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Xu X;Chen D;Feng X;Hu J;Ge J;Yan C;Zhang D;Ling Z;Chen J;Wu J
胆管细胞癌(CCA)是一种致命性极强的恶性肿瘤，死亡率极高。由于CCA发病机制的隐匿性，大多数患者诊断为晚期。然而，化疗和免疫治疗对这些患者的疗效有限。这种现象的原因尚不清楚，最近的研究表明它可能与易感遗传因素和肿瘤微环境(TME)的改变有关。TME是由肿瘤产生的，由肿瘤诱导的相互作用主导。TME中免疫细胞和间质细胞的浸润程度可能影响肿瘤的预后。通过CiberSort算法得到每个样本的免疫细胞丰度比，并使用估计计分系统计算CCA中的免疫和间质评分。根据免疫/间质评分将TCGA数据库中的CCA病例分为高、低两组。然后，我们鉴定了两组差异表达基因(Deg)。对DEGS进行了功能浓缩分析和蛋白质-蛋白质相互作用网络分析。有趣的是，我们发现载脂蛋白B(APOB)是这些基因中下调最多的。然后对包含100例CCA的CCA肿瘤芯片进行APOB的免疫组织化学染色，发现APOB在CCA标本中表达下调。因此，我们通过定时器对CCA的TME中的APOB函数进行了评估。结果表明，载脂蛋白B的表达可以影响免疫细胞在CCA中的渗透程度，并且载脂蛋白B的表达可能通过DNA甲基化来介导。我们的研究不仅表明APOB是CCA免疫治疗的潜在靶点，而且为研究人员探索各种肿瘤的免疫治疗提供了新的思路。
Cholangiocarcinoma (CCA) is a kind of devastating malignancy, which is correlated with the extremely high mortality. Due to the occult pathogenesis of CCA, most patients are diagnosed in the advanced stage. However, the efficacy of chemotherapy and immunotherapy is limited for these patients. The cause for this phenomenon is unclear, the recent researches indicate that it could be related to predisposing genetic factors and tumor microenvironment (TME) changes. The TME is created by the tumor and dominated by tumor-induced interactions. And the tumor prognosis could be influenced by the extent of infiltrating immune cells and stromal cells in TME. The abundance ratio of immune cells for each sample was obtained via the CIBERSORT algorithm, and we used ESTIMATE score system to calculate the immune and stromal scores in CCA. The CCA cases in TCGA database were categorized into high and low score groups according to their immune/stromal scores. And then, we identified the differential expressed genes (DEGs) in two groups. Functional enrichment analysis and protein‐protein interaction networks were carried out for DEGs. Interestingly, we found out that apolipoprotein B (APOB) is the most down-regulated among these genes. Then we performed the immunohistochemistry staining of APOB in a CCA tumor microarray which contained 100 CCA cases, APOB was down-regulated in CCA samples. Thus, we evaluated the APOB function in the TME of CCA through TIMER. The results demonstrate that the infiltration degree of immune cells in CCA could be influenced by the expression of APOB, and the APOB expression could be mediated by DNA methylation. Our study not only indicates APOB is a potential target for CCA immunotherapy but also provides new ideas for researchers to explore the immunotherapy of various tumors.
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影响因子：
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作者：
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DOI：
10.18632/aging.101415
发表时间：
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期刊：
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DOI：
10.1002/hep.27707
发表时间：
2015-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
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作者：
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