Abstract 316P
Background
The involvement of solute carriers in the tumorigenesis of clear cell renal cell carcinoma (ccRCC) has been popularized over the past decade. An ongoing field of research is investigating the prognostic utility of such genes. We present a multi-omics approach to tackle the prognostic value of SLC7A5 in ccRCC.
Methods
The Cancer Genome Atlas Program (TCGA) database was accessed to obtain a cohort of ccRCC patients and their corresponding clinicopathological variables and transcriptome profiles. The prognostic role of SLC7A5 expression was investigated using Kaplan-Meier survival curves augmented with multivariate Cox regression analysis. The modulated immune pathways impacted by SLC7A5 expression were explored using LinkedOmics. The tumor immune microenvironment components were studied using Tumor Immune Estimation Resource (TIMER 2.0).
Results
High SLC7A5 expression was associated with poor prognosis in ccRCC (HR: 1.991, 95% CI: 1.266-3.131, P = .003). Gene set enrichment analysis (GSEA) of SLC7A5 co-expressed genes rendered a significant modulation of multiple immune related pathways including acute inflammatory response, humoral immune response, type 2 immune response, lymphocyte mediated immunity, and interferon-gamma production. The SLC7A5 expression correlated slightly with immune suppressive cells infiltrations as in regulatory T-cells (ρ = 0.187, P < .001), myeloid-derived suppressor cells (ρ = 0.216, P < .001), cancer-associated fibroblasts (ρ = 0.343, P < .001), and M2 macrophages (ρ = 0.119, P < .05). Significant weak correlations between SLC7A5 expression and immune checkpoint genes as in CTLA-4 (ρ = 0.157, P < .001), LAG-3 (ρ = 0.187, P < .001), and PD-1 (ρ = 0.184, P < .001) were detected.
Conclusions
High SLC7A5 expression is an independent poor prognostic indicator in ccRCC. A potential immune modulatory effect of SLC7A5 was detected. Further studies are warranted to investigate the molecular mechanisms involved in its poor prognostic signature.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.