Expression of PBRM1 as a prognostic predictor in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitor
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PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment.
We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan–Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC.
Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively.
The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.
KeywordsPBRM1 Metastatic renal cell carcinoma Prognosis Sunitinib Sorafenib
This study was supported by Grant number 18ZR1423200 form Shanghai Science and Technology Commission Research Project, PYXJS16-008 from the Incubating Program for Clinical Research and Innovation of Renji Hospital, 16CR3062B from 3-year action program of Shanghai Hospital Development Center.
Compliance with ethical standards
Conflict of interest
All the authors declare no conflict of interest.
Human and animal participant rights statement
All the procedures performed in studies involving human participants were in accordance with the ethical standards of the Renji Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
- 3.Ko JJ, Xie W, Kroeger N et al (2015) The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol 16(3):293–300. https://doi.org/10.1016/s1470-2045(14)71222-7 CrossRefPubMedGoogle Scholar
- 15.Kim SH, Park WS, Park EY et al (2017) The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: a retrospective study of tissue microarrays using immunohistochemistry. PLoS ONE 12(6):e0179610. https://doi.org/10.1371/journal.pone.0179610 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Kapur P, Peña-Llopis S, Christie A et al (2013) Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol 14(2):159–167. https://doi.org/10.1016/s1470-2045(12)70584-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Cai W, Kong W, Dong B et al (2017) Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first-line therapy for Chinese patients with metastatic renal cell carcinoma. Chin J Cancer 36(1):64. https://doi.org/10.1186/s40880-017-0230-7 CrossRefPubMedPubMedCentralGoogle Scholar