Supplementary Table S1. The REMARK profile: variables, patients, and analyses Study and marker Remarks Markers m1 = interleukin-6 expression (positive or negative), m2 = interleukin-6-receptor expression (positive or negative) Future variables v1 = renal cell carcinoma morphotype, v2 = age at surgery, v3 = gender, v4 = ECOG-PS, v5 = pT stage, v6 = Fuhrman grade, v7 = tumor size, v8 = coagulative necrosis, v9 = MVI, v10 = sarcomatoid features, v11 = symptomatic presentation, v12 = rhabdoid differentiation, v13 = surgery, v14 = multifocality* Outcomes 10-year CSS, 5-year CCSS Patients n Remarks Assessed for eligibility 465 Disease: Renal cell carcinoma Patient source: Surgery 2001 to 2004, Zhongshan Hospital of Fudan University Sample source: Archived formalin fixed, paraffin embedded specimens available Excluded† 183 General exclusion criteria: Deficient follow-up, n=51; unreached clinical records, n=11; poor tumor sample preservation for TMA, n=70; unqualified HE section, n=15; suspicious death (died within 1 months after surgery), n=3; extensive necrosis (more than 50% or with massive hemorrhage), n=16; inadequate control staining or ambiguous marker staining, n=12. Un-expected therapy: Previously treated with cytokine, n=4; merely open biopsy, n=1. Included 282 Untreated before surgery. Treatment after surgery: 154 of 202 (76.2%) pT1-2N0M0 patients and 61 of 63 (96.8%) pT3-4N0M0 patients had open- or laparoscopic- radical nephrectomy, the others had partial nephrectomy, and none received adjuvant therapy after surgery; 3 bilateral tumor patients (all belong to pT1-2N0M0) had nephron-sparing surgery. All 17 (100%) pN1 or pM1 patients had cytoreductive nephrectomy, followed by immunotherapy with IFN-α or IL-2 during first year; among these patients, 7 (41.2%) had targeting agents records, all 5 pN1 patients had lymph node dissection. Clear cell renal cell carcinoma 188 Central reviewed in blind method, according to 2014 EAU guidelines Localised 180 pN1 or pM1 patients were considered metastatic RCC, n=8 Statistical analyses Events Patients Variables considered Results/Remarks A1: Interaction: markers/variables and 91 282 m1, m2, v1 to v14 Table 2 53 180 m1, m2, v1 to v13 Table 3, Figure 1 (stratified by v1) 53 180 m1, m2, v1 to v13 Table 4 (A reduced model was fitted with variables that had a P<0.05 CSS A2: Survival analyses: variables and CCSS A3: Multivariable analyses: markers/variables and CCSS A4: K-M survival analyses: markers based on the full model) 53 180 m1, m2, v5 Figure 1 (stratified by v5) 53 180 m1, m2, v4 to v8 Figure 2 (v4 to v6 integrated into UISS, v5 to v8 integrated into SSIGN) and CSS A5: Models comparison: models and CCSS Abbreviation: CSS, cancer-specific survival; CCSS, conditional cancer-specific survival; ECOG-PS, Eastern cooperative Oncology Group performance status; MVI, microvascular invasion; UISS, The University of California Los Angeles Integrated Staging System; SSIGN, the mayo stage, size, grade, necrosis score. *Not considered for survival outcome as the effective values was relatively small. †The cases that meet several exclusion criteria were counted and recorded only once.