Abstract
BackgroundsThis 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.MethodsAXL-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.ResultsThe 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.ConclusionsAXL 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.
Highlights
Renal cancer (RC) is a common malignant tumor diagnosed in the urinary system, with approximately 76,080 new cases and 13,780 new death in the United States, 2021 [1]
Consistent with The Cancer Genome Atlas (TCGA) results, AXL was up-regulated in clear cell renal cell carcinoma (ccRCC) tumor tissues and related to significant overall survival (OS)
All of these indicated that the AXL mRNA expression was up-regulated in ccRCC samples and it was significantly associated with OS
Summary
Renal cancer (RC) is a common malignant tumor diagnosed in the urinary system, with approximately 76,080 new cases and 13,780 new death in the United States, 2021 [1]. It is necessary to better understand its potential mechanisms and found a predictor of prognosis for ccRCC patients. A growing number of evidence indicated the AXL gene played an important role in tumor development, metastasis, stem cell phenotype, drug resistance, and prognosis [7,8,9,10,11]. Previous study had shown that the AXL gene could be a downstream effector of the tumor cell Epithelial-to-mesenchymal transitions (EMTs) required by the metastasis of breast cancer [12]. As for EMT, it is a process in which the epithelial cells lose epithelial properties and acquire mesenchymal features, which contributes to tumor invasion, metastasis, and resistance to therapy. This study aimed to explore the prognostic and immunological roles of AXL gene in ccRCC for overall survival (OS). As for its potential mechanisms, the LncRNA/RNA binding protein (RBP)/AXL mRNA networks were constructed to provide some references for future researches
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