Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma

Liu, Zheng; Mao, Hanwen; Chu, Dinggai; Qin, Liang; Wang, Jiang

doi:10.7150/jca.88612

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J Cancer 2024; 15(10):3034-3044. doi:10.7150/jca.88612 This issue Cite

Research Paper

Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma

Zheng Liu¹, Hanwen Mao¹, Dinggai Chu¹, Liang Qin^2✉, Jiang Wang^2✉

1. Department of Oncology, People's Hospital of Dongxihu District, Wuhan, Hubei 430040, P.R. China.
2. Department of Orthopedic, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Citation:

Liu Z, Mao H, Chu D, Qin L, Wang J. Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma. J Cancer 2024; 15(10):3034-3044. doi:10.7150/jca.88612. https://www.jcancer.org/v15p3034.htm

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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.

Keywords: Bone metastasis, kidney renal clear cell carcinoma, immune check-point inhibitor, clinical omics data cohorts

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APA

Liu, Z., Mao, H., Chu, D., Qin, L., Wang, J. (2024). Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma. Journal of Cancer, 15(10), 3034-3044. https://doi.org/10.7150/jca.88612.

ACS

Liu, Z.; Mao, H.; Chu, D.; Qin, L.; Wang, J. Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma. J. Cancer 2024, 15 (10), 3034-3044. DOI: 10.7150/jca.88612.

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CSE

Liu Z, Mao H, Chu D, Qin L, Wang J. 2024. Clinical Implications of a Six-Protein Signature in Bone Metastasis of Renal Cell Carcinoma. J Cancer. 15(10):3034-3044.

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