Fig 1: Computational analysis for prediction of time to relapse (TTR).a Cross-validated Harrel’s C-index using random survival forest models. The variables are selected by importance using minimal depth. b Minimal depth ranking of covariates. c-d Effect of the covariate in metastasis dissemination according to the value of the covariate. The histogram corresponds to the covariate data and the vertical bars are the corresponding values of the metastasis dissemination parameter (µ) distribution according to the value of the covariate. (See Ref. A8 for more details). c CFB, specific parameter values are b = 1.04 (Relative Standard Error (RSE) = 14.90%), c = 0.22 (RSE = 24.26%) and dif = - 0.67 (RSE = 11.44%) d Saa2, specific parameter values are b = 0.32 (RSE = 32.82%), c = (RSE = 39.47%) and dif = - 0.89 (RSE = 61.98%). e ?Goodness-of-fit for the model with the effect of CFB and the data at different thresholds. f Goodness-of-fit for the model with the effect of SAA2 and the data at different thresholds. g-h Individual predictions of two patients, with probabilities to have metastasis at diagnosis or not to have metastasis after 5 years. The plot corresponds to the predicted DMFS curve for the individual patients, which allows to calculate the predicted TTR
Fig 2: Clinical relevance of SAA2 and CFB expression in patients treated with antiangiogenic therapy (SUVEGIL-TORAVA cohorts). a Association between plasma SAA2 or CFB levels at diagnosis and Progression-free survival (PFS) in patients after sunitinib or bevacizumab treatment (plasma level at diagnosis less or greater than a 2nd quartile cut-off for: SAA2 (196.83 µg/ml; HR(log-rank) = 2.309); CFB (266.03 µg/ml; HR(log-rank) = 2.078). Low, n = 45; High, n = 14 b Progression-free and overall survival (left and right, respectively) of patients, stratified according to plasma levels of SAA2 at diagnosis, after treatment with sunitinib (plasma level at diagnosis less or greater than a cut-off for SAA2 (196.83 µg/ml)(OS: HR(log-rank) = 6.922; Low, n = 30; High, n = 4. PFS: HR(log-rank) = 8.035. Low, n = 27; High, n = 4). c Three subgroups were identified i) CFB low and SAA2 low, ii) CFB low and SAA2 high or CFB high and SAA2 low, iii) CFB high and SAA2 high. Low-low vs high-high: PFS HR(log-rank) = 4.324); OS HR(log-rank) = 3.373. PFS (left graph; Low, n = 38; Low/High or High/Low, n = 14; High, n = 7) and OS (right graph; Low, n = 35; Low/High or High/Low, n = 14; High, n = 7) of patients treated with either Sunitinib or bevacizumab and stratified according to SAA2 and CFB plasma levels
Fig 3: Clinical relevance of SAA2 and CFB expression in the UroCCR cohort. a Overall Survival (OS) of patients stratified according to SAA2 (HR(log-rank) = 2.901 (1.526–5.517)) or CFB gene expression (HR(log-rank) = 2.556 (1.24–5.267); n = 89). b Disease-Free Survival (DFS) of patients stratified according to SAA2 (HR(log-rank) = 2.342 (1.211–4.529)) or CFB gene expression (HR(log-rank) = 2.846 (1.323–6.123); n = 104). c qPCR analysis of tissues deriving from primary tumors or adjacent normal tissues. d Gene expression of SAA2 and CFB in patient’s tumor tissue stratified according to low Fuhrman grade (1–2), grade 3 and grade 4, compared to adjacent normal tissues. e and f ELISA experiment showing plasma levels of SAA2 and CFB, in non-metastatic (M0) and metastatic (M1) patients at the moment of diagnosis, before and after surgery, respectively. g Disease-Free Survival (DFS) of patients stratified according to SAA2 (HR(log-rank) = 8.191 (2.04–32.891); Low, n = 9; High, n = 9) or CFB (HR(log-rank) = 2.545 (0.578–11.201); Low, n = 8; High, n = 9) plasma levels before surgery (i.e. primary tumor resection). h Overall Survival (OS) of patients stratified according to SAA2 (HR(log-rank) = Inf, not calculable) or CFB (HR(log-rank) = 0.875 (0.123–6.237)) plasma levels after surgery (i.e. primary tumor resection). Low, n = 9; High, n = 10
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