Upregulated X-C motif chemokine ligand 2 (XCL2) is associated with poor prognosis and increased immune infiltration in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most popular malignant carcinomas in the genitourinary system. As a novel tumor-related gene, X-C Motif Chemokine Ligand 2 (XCL2) was up-regulated in ccRCC. The current study aims to reveal the functional activity of XCL2 in ccRCC.

Methods: The transcriptome profiling, clinical parameters, and simple nucleotide variation profiles of ccRCC samples were obtained from the Cancer Genome Atlas (TCGA) database. The survival analysis, multivariate/univariate Cox analysis, correlation analysis, gene set enrichment analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Next, immune cell infiltration and immune functions were analyzed. Finally, the functions of XCL2 were investigated in Caki-1 and 786-O cells.

Results: Upregulated XCL2 was associated with worse overall survival of ccRCC and correlated to age, grade, stage, and T stage. Age, grade, and XCL2 were independent prognostic factors. Significant enrichment in apoptosis, DNA replication, and immune response was demonstrated by GSEA. XCL2 was not only tightly associated with immune cell infiltration, but also significantly linked with several immune functions. Moreover, patients, who had higher XCL2 expression, owned higher levels of TMB. Interestingly, XCL2 was positively correlated with common immune checkpoints. In vitro, XCL2 could inhibit apoptosis, and promote proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of Caki-1 and 786-O cells.

Conclusions: In general, the current study suggested that XCL2 may participate in the progression of ccRCC. Importantly, XCL2 may be a potential new target of immunotherapy.