103 MET ECD shedding and poor DFS Evaluation of MET ectodomain shedding in C-terminal MET positive cancers and its association with prognosis Based on the receiver operating characteristic analyses for disease-free survival and overall survival, absence of MET ectodomain shedding was defined as ectodomain shedding in <35% of cancer cells and presence of ectodomain shedding was defined as ≥35% of cancer cells (Supplementary Tables 8–11; Supplementary Figs. 7, 8). Univariable survival analyses performed for ectodomain shedding and the set of clinico-histopathological characteristics listed in Table 3 show that patients with cancers subjective to ectodomain shedding (n = 38, 36%) perform significantly worse in terms of disease-free survival (HR = 2.05; 95% CI, 1.20–3.51 and P = 0.009; Fig. 7a) and overall survival (HR = 1.83; 95%, CI 1.04–3.23 and P = 0.038; Fig. 7b). To test the independent value of MET ectodomain shedding for disease-free survival and overall survival, multivariable analyses were performed correcting for age at diagnosis, pT, pN, extranodal growth, degree of differentiated, and MET ectodomain shedding (Table 4). The results show that MET ectodomain shedding only remains significantly associated with disease-free survival (HR = 2.41; 95% CI, 1.35–4.30 and P = 0.003) opposed to overall survival (HR = 1.64; 95% CI, 0.920–2.94 and P = 0.095). Fig. 7: Kaplan–Meier curves. a Disease-free survival for all patients with cancers positive for transmembranous C-terminal MET, stratified by MET ectodomain shedding. b Overall survival for all patients with cancers positive for transmembranous C-terminal MET, stratified by MET ectodomain shedding. 4
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