Presentation Authors: Wen Cai*, Jiwei Huang, Zaoyu Wang, Yichu Yuan, Wen Kong, Jin Zhang, Yonghui Chen, Qiang Liu, Wei Xue, Yiran Huang, shanghai, China, People's Republic of
Introduction: PBRM1, BAP1 and SETD2 mutations are both located on chromosome 3p and common in clear cell renal cell carcinoma(ccRCC). The purpose of this work was to detect the influence of expression of PBRM1, BAP1 and SETD2 before treatment of Tyrosine Kinase Inhibitor on the prognosis of patients with metastatic renal cell carcinoma(mRCC).
Methods: We identified 113 mRCC patients who received first-line therapy of sunitinib or sorafenib between January 2006 to December 2016 in Renji Hospital affiliated to Shanghai Jiao Tong University school of medicine. In this retrospective single-center research, PBRM1, BAP1 and SETD2 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 SETD2, PBRM1 and BAP1 expression level, and cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index and ROC analysis.
Results: Patients with low SETD2 and PBRM1 expression level had significantly shorter median PFS (11 vs 20 months, P = 0.021; 8 vs 16 months, P = 0.041) and OS (23 vs 35 months, P = 0.019; 16 vs 29 months, P = 0.004) than those with high expression level, respectively. Both low expression of PBRM1 and SETD2 showed worst prognostic. Multivariate analysis showed that SETD2 and PBRM1 were independent predictors of PFS (HR 2.142, P= 0.002; HR 1.975, P = 0.013) and OS (HR 3.002, P < 0.001; HR 2.282, P = 0.007). The model built by the addition of combination of SETD2 and PBRM1 improved C-index (Harrell concordance index) of PFS and OS to 0.72 and 0.78. And it improved predictive accuracy of AUC (Area under the ROC curve) for OS at 12 months and 24 months to 0.869 and 0.867 compared with the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium Model) (P = 0.005; P = 0.016).
Conclusions: Expression of SETD2 combined with PBRM1 could be significant prognostic factor for mRCC patients receiving target therapy while BAP1 could not. We also proved that SETD2 combined with PBRM1 could improve predictive accuracy for overall survival outcomes. SETD2 and PBRM1 are not only potential biomarkers for treatment for mRCC, but also play an important role in controlling the development and predicting prognosis of target treatment in mRCC.
Source of Funding: This study was supported by grant number18ZR1423200 form Shanghai Science and Technology Commission Research Project, PYXJS16-008 from the Incubating Program for Clinical Research and Innovation of Renji Hospital, 16CR3062B from Three-year action program