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AXL基因在与鉴定LncRNA/RBP/AXL mRNA网络相关的透明细胞肾细胞癌中的预后价值及免疫作用。

Prognostic value and immunological role of AXL gene in clear cell renal cell carcinoma associated with identifying LncRNA/RBP/AXL mRNA networks.

作者信息

Wang Yi, Tian Ye, Liu Shouyong, Wang Zengjun, Xing Qianwei

机构信息

Department of Urology, Affiliated Hospital of Nantong University, No. 20 West Temple Road, Nantong, 226001, Jiangsu Province, China.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

出版信息

Cancer Cell Int. 2021 Nov 27;21(1):625. doi: 10.1186/s12935-021-02322-y.

DOI:10.1186/s12935-021-02322-y
PMID:34838035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8626946/
Abstract

BACKGROUNDS

This article aimed to explore the prognostic and immunological roles of AXL gene in clear cell renal cell carcinoma (ccRCC) for overall survival (OS) and to identify the LncRNA/RBP/AXL mRNA networks.

METHODS

AXL-related gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset and AXL-related pathways were identified by gene set enrichment analysis (GSEA). We performed univariate/multivariate Cox regression analysis to evaluate independent prognostic factors and the relationships between AXL and immunity were also investigated.

RESULTS

The outcomes of us indicated that the AXL mRNA expression was up-regulated in ccRCC samples and high expression of AXL was associated with worse OS in TCGA dataset (P < 0.01). Further external verification results from HPA, UALCAN, ICGC dataset, GSE6344, GSE14994, and qRT-PCR remained consistent (all P < 0.05). AXL was also identified as an independent prognostic factor for ccRCC by univariate/multivariate Cox regression analysis (both P < 0.05). A nomogram including AXL expression and clinicopathological factors was established by us and GSEA results found that elevated AXL expression was associated with the JAK-STAT, P53, WNT, VEGF and MAPK signaling pathways. In terms of immunity, AXL was dramatically linked to tumor microenvironment, immune cells, immune infiltration, immune checkpoint molecules and tumor mutational burden (TMB). As for its potential mechanisms, we also identified several LncRNA/RBP/AXL mRNA axes.

CONCLUSIONS

AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.

摘要

背景

本文旨在探讨AXL基因在透明细胞肾细胞癌(ccRCC)中对总生存期(OS)的预后和免疫作用,并鉴定长链非编码RNA(LncRNA)/RNA结合蛋白(RBP)/AXL信使核糖核酸(mRNA)网络。

方法

从癌症基因组图谱(TCGA)数据集获得AXL相关基因表达矩阵和临床数据,并通过基因集富集分析(GSEA)鉴定AXL相关通路。我们进行单变量/多变量Cox回归分析以评估独立预后因素,并研究AXL与免疫之间的关系。

结果

我们的结果表明,AXL mRNA表达在ccRCC样本中上调,且在TCGA数据集中AXL的高表达与较差的OS相关(P < 0.01)。来自人类蛋白质图谱(HPA)、UALCAN、国际癌症基因组联盟(ICGC)数据集、GSE6344、GSE14994和定量逆转录聚合酶链反应(qRT-PCR)的进一步外部验证结果保持一致(均P < 0.05)。通过单变量/多变量Cox回归分析,AXL也被鉴定为ccRCC的独立预后因素(均P < 0.05)。我们建立了一个包含AXL表达和临床病理因素的列线图,GSEA结果发现AXL表达升高与JAK-STAT、P53、WNT、血管内皮生长因子(VEGF)和丝裂原活化蛋白激酶(MAPK)信号通路相关。在免疫方面,AXL与肿瘤微环境、免疫细胞、免疫浸润、免疫检查点分子和肿瘤突变负荷(TMB)显著相关。至于其潜在机制,我们还鉴定了几个LncRNA/RBP/AXL mRNA轴。

结论

AXL在ccRCC中发挥预后和免疫作用,我们还鉴定了LncRNA/RBP/AXL mRNA轴以探讨其潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/538dd5559e7a/12935_2021_2322_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/146ef4380efe/12935_2021_2322_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/da6a0bb913fb/12935_2021_2322_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/0ade8a1fc2d1/12935_2021_2322_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/a3094ade5bd1/12935_2021_2322_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/e2bbc59d914c/12935_2021_2322_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/39d50e74fa7c/12935_2021_2322_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/25f49de5f1b5/12935_2021_2322_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/146ef4380efe/12935_2021_2322_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/da6a0bb913fb/12935_2021_2322_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/beeba46df76a/12935_2021_2322_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a2e/8626946/538dd5559e7a/12935_2021_2322_Fig9_HTML.jpg

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