Abstract
Background: In renal clear cell carcinoma, a common cancer of the urinary system, 25–30% patients are metastatic at initial diagnosis and 20–30% patients have a tendency of recurrence and metastasis after local surgery. With the rapid development of tumor immunology, immune agents have brought new directions to tumor therapy. However, no relevant studies have explored the role of immune-related genes in kidney cancer metastasis. Methods: Co-expressed metastatic immune-related differentially expressed genes (mIR-DEGs) were screened by GSE12606, GSE47352, and immunorelated genes. Then, differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analysis in KIRC were performed to determine independent prognostic factors associated, and the risk prognostic model was established. The correlation of hub mIR-DEGs with clinicopathological factors, immune invasion, and immune checkpoints was analyzed, and the expression of hub mIR-DEGs and their effect on tumor were re-evaluated by OCLR scores in KIRC. Results: By comprehensive bioassay, we found that FGF17, PRKCG, SSTR1, and SCTR were mIR-DEGs with independent prognostic values, which were significantly associated with clinicopathological factors and immune checkpoint–related genes. The risk prognostics model built on this basis had good predictive potential. In addition, targeted small molecule drugs, including calmidazolium and sulfasalazine, were predicted for mIR-DEGs. Further experimental results were consistent with the bioinformatics analysis. Conclusion: This study preliminarily confirmed that FGF17, PRKCG, SSTR1, and SCTR were targeted genes affecting renal cancer metastasis and related immune responses and can be used as potential therapeutic targets and prognostic biomarkers for renal cancer. Preliminary validation found that PRKCG and SSTR1 were consistent with predictions.
Highlights
Renal cell carcinoma (RCC) is the most common renal malignancy originating from tubular epithelium (Siegel et al, 2018)
The risk prognosis model was significantly negatively correlated with the infiltration of M2 macrophages (r −0.12, p 0.004), neutrophils (r −0.40, p 1.97e-21), CD4+ T cells (r −0.26, p 0.1.37e-09), and myeloid dendritic cells (r −0.25, p 3.91e-09) (Figures 3C,E,G,J) and significantly positively correlated with the infiltration of monocytes (r 0.22, p 4.88e-07) and uncharacterized cells (r 0.23, p 4.62e-08) (Figures 3D,K). These results indicated that the hub mIR-DEG–based risk prognosis model, including FGF17, Protein kinase C gamma (PRKCG), Somatostatin receptor 1 (SSTR1), and Secretin receptor (SCTR), had good predictive effect and was significantly correlated with the Kidney renal clear cell carcinoma (KIRC) immune microenvironment
These results suggested that FGF17, PRKCG, SSTR1, and SCTR might affect the degree of similarity between KIRC cells and stem cells, affecting tumor biological processes and degree of dedifferentiation
Summary
Renal cell carcinoma (RCC) is the most common renal malignancy originating from tubular epithelium (Siegel et al, 2018). Its characteristic is to stimulate specific immune response and inhibit and kill tumor cells, thereby reducing tumor metastasis and recurrence. The advent of immunotherapy and targeted therapy has diversified the treatment of RCC, some patients with RCC develop symptoms only when their cancer cells have metastasized to a distant point in their body, and the five-year survival rate of these patients is usually less than 20% (Dunnick, 2016). In renal clear cell carcinoma, a common cancer of the urinary system, 25–30% patients are metastatic at initial diagnosis and 20–30% patients have a tendency of recurrence and metastasis after local surgery. No relevant studies have explored the role of immune-related genes in kidney cancer metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
