American Association for Cancer Research
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FIGURE 1 from Kinase Inhibitor Pulldown Assay Identifies a Chemotherapy Response Signature in Triple-negative Breast Cancer Based on Purine-binding Proteins

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posted on 2023-08-15, 14:20 authored by Junkai Wang, Alexander B. Saltzman, Eric J. Jaehnig, Jonathan T. Lei, Anna Malovannaya, Matthew V. Holt, Meggie N. Young, Mothaffar F. Rimawi, Foluso O. Ademuyiwa, Meenakshi Anurag, Beom-Jun Kim, Matthew J. Ellis

The application of the KIPA in the CPTAC-TNBC samples. A, Overview of the 43 pretreatment biopsy samples used in this study (14 pCR samples and 29 non-pCR samples). The biopsy samples were accrued from patients with TNBC enrolled in two clinical trials (NCT02547987 and NCT02124902) who were treated with six cycles of docetaxel and carboplatin (14). pCR, RCB class, omics data availability, and molecular subtypes were obtained from previous publication (16) and are indicated via color-coded annotation tracks. B, The workflow of KIPA was similar as described previously (13). Native lysates from OCT-embedded biopsy samples were incubated with homemade kinobeads (9 inhibitor bead cocktail) for 1 hour, followed by multiple washing steps and in-solution digestion. Quantitative MS was used for accurate identification and quantification. C, Protein classes of total 2,641 proteins detected by KIPA in 43 biopsy samples. KI-L, lipid kinase; KI-P, protein kinase, KI-M, metabolic kinase, KI-X, uncategorized kinase. D, Top 20 molecular function terms of GO ORA with a total of 2,641 proteins detected by KIPA. The color of each dot represents the significance (P-value) of enrichment, and the size is proportional to the overlapping number between 2,641 proteins and each term (also indicated by the labeled number). The red text denotes kinase-associated function while green denotes nucleotide-associated functions.

Funding

HHS | NIH | National Cancer Institute (NCI)

Cancer Prevention and Research Institute of Texas (CPRIT)

History

ARTICLE ABSTRACT

The identification of pretreatment predictive biomarkers for pCR in response to neoadjuvant chemotherapy would advance precision treatment for TNBC. To complement standard proteogenomic discovery profiling, a KIPA was deployed and unexpectedly identified a seven-member non-kinase PBP pCR-associated signature. Individual members served diverse pathways including IFN gamma response, nuclear import of DNA repair proteins, and cell death.