LncRNA ADAMTS9-AS1 as a Potential Biomarker for the Infiltration of Immunosuppressive Cells in Kidney Carcinoma

Abstract

Background: Dysregulation of ADAMTS9-AS1 is engaged in the carcinogenesis and metastasis of different cancers. However, whether ADAMTS9-AS1 dysregulation may have an impact on the prognosis and tumor lymphocytes infiltration in kidney cancer remains unclear. Methods: Data from the cancer genome atlas (TCGA) were used to assess ADAMTS9-AS1 expression pattern in different cancers. Survival rates of patients with different tumors (with a focus on kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP)), and ADAMTS9-AS1 expression level were subjected to Cox regression and Kaplan-Meier curve analysis. Associations of ADAMTS9-AS1 expression with clinicopathological parameters were determined by Wilcoxon singed-rank test. ADAMTS9-AS1 expression prognostic potential was evaluated with univariable and multivariable Cox analyses. Gene set enrichment analysis (GSEA) and pathway enrichment analysis were used to determine pathways and gene sets associated with ADAMTS9-AS1 expression level. Tumor microenvironment and immune cell infiltration were assessed using Estimate and cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) methods. Results: ADAMTS9-AS1 was downregulated in KIRC, and was associated with a poor survival. Low ADAMTS9-AS1 expression level in KIRC was associated with more advanced clinical stages, larger tumor sizes, more metastases and higher histological grades. In contrast, ADAMTS9-AS1 was overexpressed in KIRP which was associated to better survival rate. Low ADAMTS9-AS1 level in KIRP was associated with more advanced clinical stages, larger tumor sizes, and more lymph node metastases and distant metastases. GSEA analysis showed that histidine metabolism and autophagy pathway regulation were enriched in ADAMTS9-AS1 high expression group of KIRC and KIRP. In addition, regulatory T cell (Treg) markers, including Forkhead Box O3 (FOXO3) and transforming growth factor-β1 (TGFβ1), were negatively correlated with ADAMTS9-AS1 level. Low ADAMTS9-AS1 expression was associated with macrophage and Treg enrichment in KIRC and KIRP. Conclusion: ADAMTS9-AS1 may be used as a potential biomarker to indicate the infiltration of immunosuppressive cells in KIRC and KIRP.