Fig. 4: Impact of high cMET but not RAS pathway activity on clinical outcome of triple-negative breast cancer patients in cooperation with RB-loss. | Nature Communications

Fig. 4: Impact of high cMET but not RAS pathway activity on clinical outcome of triple-negative breast cancer patients in cooperation with RB-loss.

From: Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer

Fig. 4: Impact of high cMET but not RAS pathway activity on clinical outcome of triple-negative breast cancer patients in cooperation with RB-loss.The alternative text for this image may have been generated using AI.

a Expression of a cMET signature, MET24, developed for hepatocellular carcinomas (HCC), in indicated molecular breast cancer subtypes, with highest level in basal-like breast cancer. In a, d, i, P = 0.0000 denotes P < 0.0001, using PRISM and two-tailed, unpaired t test; error bars represent SD. b Kaplan–Meier disease-free (DFS) and overall (OS) survival curves for breast cancer patients segregated based on MET24 signature level. HR denotes hazard ratio. P values in b, e, h calculated by Log-rank (Mantel–Cox) test. c cMET signature expression in 6 and 4 different triple-negative breast cancer (TNBC) subtype classification with highest expression in BL1 together with RBKO high, PI3K-, MYC-, WNT-, RAS- and RHOA-signaling high and PTEN and TP53 loss. MET24-high samples overlap with the most aggressive TNBC lesions (demarcated by the red box), defined by PTEN-loss and 5 miRNA-low (PTENlow/miRlow, red) as described70. BL1 Basal-like 1, BL2 Basal-like 2, M mesenchymal, MSL mesenchymal stem–like, IM immunomodulatory, LAR luminal androgen receptor, UNS unspecified. d Levels of MET24 and RAS signatures in the different TNBC subtypes. MET24 is significantly higher in BL1 versus other subtypes; RAS pathway activation is seen in BL1, BL2 and MSL. e Kaplan–Meier OS curves showing MET but not RAS pathway activity identifies TNBC with unfavorable prognosis. f Kaplan–Meier OS curve showing MET pathway-high identifies BL1 TNBC patients with exceedingly poor prognosis. g OS curve of an independent cohort showing MET pathway-high segregates BL1 but not all TNBC patients into relatively fair versus poor prognosis. h Effect of RB loss, MET signature high or both on OS of TNBC patients in the SCAN-B 327 TNBC cohort. Analysis of two additional cohorts is shown in supplementary Fig. S3. i Heat map and graphic presentation of MET24, RAS and RHOA signature levels in breast cancer cell lines classified by PAM50. Cell lines marked in red were used to characterize gCISs; those marked by asterisks were used to test the effect of RB depletion on cell migration.

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