ABSTRACT
Bone metastases is prevalent from renal cell carcinoma (RCC) with poor quality of life and prognosis. Our previous proteomics analysis identified dysregulated proteins in the bone-tropism RCC cells. In this study, we further examined the clinical implications of these proteins using multiple clinical cohorts. We identified 6 proteins with significant upregulation in RCC tumor tissue in comparing to tumor adjacent normal tissue (p<0.05). High expression of these 6 protein-encoding genes significantly correlates with a poor survival in the TCGA-KIRC (Kidney renal clear cell carcinoma) cohort (log-rank test p=2.7e-05), and they all individually had a reverse-correlation with the gene expression of VHL and PBRM1 (p<0.001), and positive-correlation with the expression of VEGFA (p<0.001). Further gene set variation analysis (GSVA) revealed positive correlation with Th17 cells enrichment and negative CD8 T cell infiltration in the RCC tumor microenvironment. High expression of these 6 genes in pretreatment tumors favors longer overall survival (OS)(p=0.027) in anti-PDL1 treated patients (n=428). We treated one humeral metastases RCC patient with the anti-PDL1 antibody drug atezolizumab after examined the elevated expression of the 6 proteins in his nephrectomy tumor tissue, the tumor at the fracture site shrunk remarkably after four courses of treatment. These results altogether suggest a clinical implication of the 6-protein signature in RCC bone metastasis prognosis and response to immune-checkpoint inhibitor treatment.
