作用于 RNA 1 (ADAR1) 的腺苷脱氨酶是一种 RNA 编辑酶，可显着影响癌症进展和各种生物过程。使用癌症基因组图谱 (TCGA) 数据集检查了多种癌症类型中 ADAR1 mRNA 的表达，揭示了肾嫌色细胞 (KICH)、肾肾透明细胞癌 (KIRC)、肾肾乳头状细胞癌 (KIRP)、和肝细胞癌（LIHC）与正常对照相比。然而，这些差异表达的原因仍不清楚。在本研究中，我们进行了 RT-PCR 和蛋白质印迹 (WB) 来验证临床组织样本中 ADAR1 的表达模式。使用TCGA数据进行生存分析和免疫微环境分析（包括免疫评分和基质评分），以确定与ADAR1相关的特定细胞类型，以及这些细胞类型中的关键基因。使用临床肝癌和肾癌样本，通过免疫组织化学 (IHC) 验证 ADAR1 与特定细胞类型关键基因之间的关系。我们的验证分析显示，与相比，ADAR1 在 KICH、KIRC 和 KIRP 中表达下调，而在 LIHC 中表达上调正常组织。值得注意的是，ADAR1 mRNA 表达与患者预后之间存在显着相关性，特别是在 KIRC、KIRP 和 LIHC 中。有趣的是，我们在 KIRC 中观察到 ADAR1 表达与基质评分之间呈正相关，而在 LIHC 中观察到负相关。细胞类型分析强调了 ADAR1 表达与两种基质细胞类型（血液内皮细胞 (BEC) 和淋巴内皮细胞 (LEC)）之间的独特关系，并进一步确定了 KIRC 和 LIHC 中的特征基因claudin-5 (CLDN5)。此外，通过 IHC 验证，ADAR1 在 KIRC (n = 26) 和 LIHC (n = 30) 样本中与 CLDN5 呈负相关。ADAR1 在 LIHC 和 KIRC 中起着相反的作用，与肿瘤内 BEC 和 LEC 的富集相关。这项研究揭示了基质细胞在复杂的肿瘤微环境 (TME) 中的重要作用，并为肿瘤免疫治疗和精准医学的未来研究提供了新的见解。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that significantly impacts cancer progression and various biological processes. The expression of ADAR1 mRNA has been examined in multiple cancer types using The Cancer Genome Atlas (TCGA) dataset, revealing distinct patterns in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC) compared to normal controls. However, the reasons for these differential expressions remain unclear.In this study, we performed RT-PCR and western blotting (WB) to validate ADAR1 expression patterns in clinical tissue samples. Survival analysis and immune microenvironment analysis (including immune score and stromal score) were conducted using TCGA data to determine the specific cell types associated with ADAR1, as well as the key genes in those cell types. The relationship between ADAR1 and specific cell types' key genes was verified by immunohistochemistry (IHC), using clinical liver and kidney cancer samples.Our validation analysis revealed that ADAR1 expression was downregulated in KICH, KIRC, and KIRP, while upregulated in LIHC compared to normal tissues. Notably, a significant correlation was found between ADAR1 mRNA expression and patient prognosis, particularly in KIRC, KIRP, and LIHC. Interestingly, we observed a positive correlation between ADAR1 expression and stromal scores in KIRC, whereas a negative correlation was observed in LIHC. Cell type analysis highlighted distinct relationships between ADAR1 expression and the two stromal cell types, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and further determined the signature gene claudin-5 (CLDN5), in KIRC and LIHC. Moreover, ADAR1 was inversely related with CLDN5 in KIRC (n = 26) and LIHC (n = 30) samples, verified via IHC.ADAR1 plays contrasting roles in LIHC and KIRC, associated with the enrichment of BECs and LECs within tumors. This study sheds light on the significant roles of stromal cells within the complex tumor microenvironment (TME) and provides new insights for future research in tumor immunotherapy and precision medicine.Copyright © 2024 Elsevier B.V. All rights reserved.