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FIGURE 2 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

Differential protein analysis between pCR and non-pCR samples. A, Volcano plot shows results from differential analysis between pCR and non-pCR samples with the KIPA. X-axis is the log10 fold change between median value of pCR and non-pCR samples for each protein. Y-axis is the −log10P-value from Wilcoxon rank-sum tests comparing protein levels in pCR samples to non-pCR samples. Red and blue points indicate the most significant (P < 0.01) proteins, and pink and light blue points indicate significant (0.01 < P < 0.05) proteins. B, Heat map shows the levels of seven PBP signature genes across 43 samples, arranged by RCB class (0, I, II, II) and the KIPA-based PBP signature score. The levels of seven genes were assessed at the level of KIPA (orange), protein (light blue), and mRNA (pink), and normalized across all samples by z-score. P values were determined by Wilcoxon rank-sum tests comparing gene levels for pCR samples to non-pCR samples. PBP signature, purine-binding protein signature.

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.