Cytokines in Renal Cell Carcinoma : With emphasis on Vascular Endothelial Growth Factor (VEGF) and Interleukin 6 (IL-6)

Aims: In the first three papers we aimed to investigate if different circulating cytokines in blood drawn preoperatively can predict outcome after surgery in patients with renal cell carcinoma (RCC). The last paper aimed to evaluate the volatility of different cytokines and their receptors before, during and after surgery. Material and Methods: In the three first studies (paper I-III), we used data from our kidney cancer database at Haukeland University Hospital. From the database, we identified 159 patients treated with partial, radical or a cyto-reductive nephrectomy at our institution between January 2007 and March 2010, who had signed informed consent forms and a preoperative drawn frozen blood sample were available. In the last study (paper IV), 40 patients with renal tumors who were scheduled for open surgery with partial or radical nephrectomy were prospectively included between April 2018 and June 2019. Blood samples were taken pre-operatively, intra- operatively (simultaneously from the renal vein (RV) and a peripheral vein) and at control 4-6 weeks post-surgery. The blood samples in all papers were analyzed and cytokines detected and measured using Luminex immune-bead technology and high-sensitivity kit from Invitrogen/Biosource. In paper I-III, the patients were followed up until death or the end of each study period. Results: In paper I, a high level of circulating VEGF were an independent predictor (p=0.017) for cancer specific survival (CSS) in a multivariate analysis. Furthermore, VEGF together with the well-established prognostic factors tumor T-stage and nuclear grade, predicted disease recurrence in patients presumed to be radically treated (p=0.03, p=0.011 and p=0.008, respectively). In paper II, a high level of IL-6 and IL-27 predicted disease recurrence in presumed radically treated patients (p=0.001 and p=0.026, respectively). In particular, the predictions among patients with large tumors (>7 cm) were excellent for both IL-6 and IL-27 (p=0.014 and p=0.001, respectively). In paper III, ...