Fig. 6: Proteasome activity is associated with malignancy and serves as a predictive marker for MDR.

a, b Pan-cancer data from TCGA and TARGET comparing the proteasome activity scores (expression levels of proteasome genes, n = 45) in indicated tissues (a) or tumor stages (b). c, d The proteasome activity for breast cancer patients (n = 65) was detected by our kit, and proteasome activities in indicated breast cancer subtypes or tumor stages were compared. e The comparison of proteasome activities in resistant patients (PD) and sensitive patients (PR and SD) with breast cancer (n = 25). Stable and progressive disease following chemotherapy were evaluated based on the changes in tumor burden according to the RECIST guideline (v1.1). f The proteasome activity for colon cancer patients (n = 42) was detected by our kit and compared between indicated tumor stages. g The comparison of proteasome activities in resistant patients (PD) and sensitive patients (PR and SD) with colon cancer (n = 58). h–j Nude mice bearing 231-R3 multidrug-resistant cells were treated with vehicle, CIS (3 mg/kg) or CIS plus CFZ (1 mg/kg) every 3 days for 7 times, and tumor photograph and tumor weight were recorded (h). K48 polyUB in tumors was detected by IHC staining (i), and proteasome activity in tumors were detected by our kit (j). k Tumor slices were prepared from a breast cancer patient at stage IV and treated with the indicated drugs alone or in combination with CFZ. Slice viability was assessed by MTT staining. l Treatment procedure and responses of a breast cancer patient from surgery through proteasome activity assessment, followed by treatment with a proteasome inhibitor IXA. m, n Proteasome activity was tested in eight patients who did not achieve pathological complete response (non-pCR) (m); and the patient with the highest proteasome activity was sampled for PDO culture and screening of 52 drugs (n). o Tumor CT scan images and photos of the tumor site show that the malignant ascites and the tumor were shrunken during the GEM plus IXA treatment. All values are presented as mean value (at least three replicates) ± SD, and P value was calculated by comparison with the Ctr group or indicated separately (two-tailed Student’s t-test, *P < 0.05, **P < 0.01, ***P < 0.001).