Prognostic value of plasminogen activator inhibitor‐1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib

Abstract

Background and Aims Vascular endothelial growth factor‐directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers. Methods From September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4 weeks after axitinib initiation. Bio‐Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation. Results Patients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor‐1 (PAI‐1) level from pre‐treatment to 4 weeks after axitinib initiation compared with those with progressive disease ( P = .022). The median progression‐free survival (PFS) and median overall survival (OS) in patients with increased serum PAI‐1 level from pre‐treatment to 4 weeks after axitinib initiation were significantly shorter than those with decreased serum PAI‐1 level ( P = .027 and P = .026, respectively). Increased serum PAI‐1 level from pre‐treatment to 4 weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses ( P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI‐1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis ( P = .026 and P = .010, respectively). Conclusions The initial change in serum PAI‐1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC.